Open Access

Common methods in mitochondrial research (Review)

  • Authors:
    • Yiyuan Yin
    • Haitao Shen
  • View Affiliations

  • Published online on: August 19, 2022     https://doi.org/10.3892/ijmm.2022.5182
  • Article Number: 126
  • Copyright: © Yin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mitochondrial abnormalities are primarily seen in morphology, structure and function. They can cause damage to organs, including the heart, brain and muscle, by various mechanisms, such as oxidative stress, abnormal energy metabolism, or genetic mutations. Identifying and detecting pathophysiological alterations in mitochondria is the principal means of studying mitochondrial abnormalities. The present study reviewed methods in mitochondrial research and focused on three aspects: Mitochondrial extraction and purification, morphology and structure and function. In addition to classical methods, such as electron microscopy and mitochondrial membrane potential monitoring, newly developed methods, such as mitochondrial ultrastructural determination, mtDNA mutation assays, metabolomics and analyses of regulatory mechanisms, have also been utilized in recent years. These approaches enable the accurate detection of mitochondrial abnormalities and provide guidance for the diagnosis and treatment of related diseases.

1. Introduction

Mitochondria are semi-autonomous organelles found in most eukaryotic cells with a bilayered structure consisting of an outer membrane, an intermembrane space and an inner membrane. They serve key roles in a variety of cellular processes, including cell metabolism, signal transduction and the regulation of cell death. Mitochondria have numerous biological functions, including the production of ATP for cellular energy, regulation of the dynamic balance of intracellular Ca2+, production of reactive oxygen species (ROS), the release of cytochrome c and regulation of intracellular environmental homeostasis. As an important signaling hub in cells, the mitochondrion serves a key role in diseases such as aging and obesity. Mitochondrial biogenesis and mitochondrial homeostasis require the expression of nuclear genes and mitochondria-nuclear signaling pathways to be regulated (1). On the one hand, it depends on the regulatory pathways of nuclear gene transcription and anterograde signaling. Mitochondria, on the other hand, pass intracellular signaling molecules, such as Ca2+, mitochondrial DNA (mtDNA), reactive oxygen species (ROS), adenosine triphosphate (ATP), coenzyme Q (CoQ) and nicotinamide adenine dinucleotide (NAD) and then present mitochondrial abnormalities and cellular metabolic change signals to the nucleus (retrograde signaling). This triggers the nucleus to activate important signaling pathways by mobilizing a series of nuclear transcription factors (2-5), mitochondrial transcription and mitochondrial biosynthesis. Among them, the activation of signaling pathways is closely related to inflammation and tumorigenesis (6). During cellular stress and virus infection, mtDNA and ROS are released from abnormal mitochondria and retrogradely presented to the nucleus as danger signals. The nucleus can promote the expression of PTEN-induced kinase 1 (PINK1) and then upregulate mitophagy to clear abnormal mitochondria and maintain a stable intracellular environment. When too many abnormal mitochondria cannot be completely removed, mtDNA can activate Toll-like receptor 9 (TLR9) and its downstream inflammatory pathways and lead to inflammation. Excessive ROS can cause DNA damage by oxidizing nucleic acid bases, which is closely related to tumorigenesis. Abnormalities in mitochondrial structure and function can lead to a variety of intracellular signaling cascades, oxidative stress and the initiation of programmed cell death, thereby contributing to the development and progression of nearly all diseases. Therefore, the detection of mitochondrial abnormalities is crucial and various mitochondrial assays (Fig. 1) developed in the last century have contributed substantially to the differential diagnosis of mitochondrial diseases. The present study reviewed common experimental methods (Table I) in mitochondrial research. In particular, it discussed a wide range of imaging and detection techniques for i) extraction and purification, ii) analyses of morphology and structure and iii) analyses of function, with a focus on the clinical implications for disease detection and treatment.

Table I

Summary of mitochondrial research methods.

Table I

Summary of mitochondrial research methods.

Area of researchMethodsScope of applicationAdvantagesDrawbacks
Extraction and purification ofDifferential centrifugation extractionTissues and cellsDetect mitochondrial morphological structureLow mitochondrial purity
mitochondriaDensity gradient centrifugationSucroseLow cost and wide applicationPoor mitochondrial morphological integrity
purification (different media)PerollIsolate platelet mitochondriaHigher cost compared to sucrose
NycodenzCompared to sucrose, higher density and lower viscosity without affecting osmotic pressure
OptiprepAutomatic gradients can be formed in a short time
Magnetic bead methodTissues and cellsMitochondrial purity and integrity superior to other methodsNot yet widely used
Mitochondrial morphologyElectron microscopeGold standardCannot clearly distinguish mitochondria from other membranous structures
AiryScan microscopeObservable mitochondrial dynamicsNot yet widely used
Atomic force microscopeObservation of mitochondrial swelling and mitochondrial dynamics
3D Confocal MicroscopyThicker cellsFor thicker cells
Mitochondrial functionMitochondrial membrane potentialRhodamine 123, JC-1 TMRM, TMRE TRR-CYTissues and cellsIntuitively reflect changes in MMPHigh cytotoxicity
Low cytotoxicity for quantitative analysis of MMPsNot yet widely used
Extremely sensitive to detect minute changes in MMP
FRETMonitoring dynamic changes of MMP
Mitochondrial oxygen consumptionOxygen electrode polarographyTissues and cellsLow cost, detection of respiratory control ratePoor specificity
Hippocampus analyzerComprehensive analysis of mitochondria by measuring oxygen consumption rateCan be affected by chemicals such as phenol red
Mitochondrial Ca2+ DetectionElectrochemical analysisSuitable for experiments with low sensitivity, unable to distinguish mitochondrial Ca2+ from total Ca2+Poor specificity
Calcium-Rhodamine 123Tissues and cellsHigh specificity, suitable for the detection of mitochondrial Ca2+ in various living cellsInability to distinguish between different cellular sources of Ca2+
Fluo-3Distinguish mitochondrial Ca2+ from Ca2+ in other intracellular organelles
Mitochondrial membrane permeability transition poreFully automatic patch clampSuspension cellsCan be used for detection of suspension cellsSmall scope of application
Calcein-AMTissues and cellsStrong specificity, can reflect the opening degree of mPTP in real timeEasy to be quenched, timely observation is required
Mitochondrial ATPHigh pressure liquid chromatographyTissues and cellsCan detect differences in cellular energy substances in different statesRequires a larger sample size
Enzymatic analysisIt is greatly affected by the absorbance of the tested sampleSusceptible to redox reactions
Fluorescence analysisThe amount of luminescence is proportional to ATPEasy to quench
Mito-RhCan specifically recognize ATP in mitochondria
Mitochondrial functionMitochondrial respiratory chain complex SpectrophotometryTissues and cellsWide range of applications, but less accurateVulnerable to external biochemical interference
NIR spectroscopy non-invasive measurementsLess affected by the outside world, high accuracyRequires a very large sample size
ROSChemical reaction selective electrode methodTissues and cellsHigh sensitivity, cheap and easy to operate, but poor specificity and unstable resultsPoor specificity and unstable results
SpectrophotometryHigh sensitivity and specificity, but cannot perform localization analysis of oxygen free radicalsUnable to perform localization analysis of oxygen free radicals
Reagent test kitStrong specificity, easy operation, low background, large detection range, easy quenchingEasy to quench
Electron spin resonanceThe most direct and effective, expensive and complicated operationExpensive and complicated to operate
Mitochondrial DNAPCRTissues and cellsDetectable mtDNA deletionsThe presence of mtDNA heterogeneity in the primer binding region
FISHVisually detectable under a fluorescence microscopePoor specificity and insufficient hybridization
SequencingGold standard for detecting heterogeneityLimited to small scale projects
Probe methodDetect mtDNA dynamic changesNeed real-time observation

[i] TMRM, tetramethyl rhodamine methyl ester; TMRE, tetramethyl rhodamine ethyl ester; FRET, fluorescence resonance energy transfer; FISH, fluorescence in situ hybridization; MMP, mitochondrial membrane potential; mtDNA, mitochondrial DNA.

2. Extraction and purification of mitochondria

A suitable method is needed to extract purified mitochondria from various tissues and cells (7). The basic extraction method mainly relies on differential centrifugation, while purification mainly depends on density gradient centrifugation. The specificity of tissue cells determines the details of the method (8-10).

Extraction of mitochondria

When extracting mitochondria, because the homogenization process can heat the sample locally, resulting in protein denaturation and aggregation, the equipment must be pre-cooled and the temperature kept low throughout the process (11). Tissue or cell homogenization is followed by continuous differential centrifugation. Unlysed cells, cell debris and nuclei are first removed by low-speed centrifugation (600 × g or 1,000 × g) (12-15). As mitochondria can remain in flaky precipitates generated by low-speed centrifugation, resuspending the pellet and centrifuging it again at low speed increases mitochondrial yield. The supernatant obtained by two low-speed centrifugation steps is collected for high-speed centrifugation (3,500 × g or 10,000 × g) (12-15), resulting in a coarse-lifted mitochondria precipitate (16). The purity of these crudely extracted mitochondria can meet some applications, including the analysis of the activity of known mitochondrial proteins, the detection of mitochondrial morphology and mitochondrial apoptosis; however, they often contain a certain amount of peroxisomes, endoplasmic reticulum and microsomes. Mitochondrial purity is low; thus, mitochondrial purification and reduction of membrane fouling are required when analyzing proteins present in multiple cells or determining the localization of a protein (17). Furthermore, although the mitochondrial extraction method is suitable for most tissues and cells, the extraction efficiency and quantity of mitochondria in different tissues and cells are significantly different. This is determined by the number of mitochondria in the tissue or cell and the energy consumption of muscles and liver; larger tissues contain more mitochondria, so these tissues and cells have higher mitochondrial extraction efficiency than other tissues, such as the lungs (18-20).

Purification of mitochondria

Purified mitochondria are the prerequisites for mitochondrial proteomics research. Density gradient centrifugation emerged in the 1950s and has become a common method for separating extracts owing to its ease of operation and low cost (21). For example, sucrose density gradient centrifugation suspends the cell or a homogeneous tissue slurry in a uniform suspension medium according to the density of each cell component and is separated by differential centrifugation (22-24). The buffered sucrose solution, the most commonly used suspension medium, is relatively close to the dispersion phase of the cytoplasm and can maintain the structure of various organelles and the activity of enzymes to a certain extent (25-28).

Sucrose density gradient centrifugation is a classic method for extracting mitochondria by separating cellular fractions of different densities (29). It involves three main processes: Tissue homogenization, fractionation and analysis (30-32). Homogenization refers to the disruption of cells or tissues in a homogenizer by adding sucrose at a low temperature to form a homogenate containing various organelles and other substances (33). Fractionation is the sequential settling of particles of different densities and sizes in the sample by centrifugation at different speeds. Analysis refers to the use of biochemical methods to identify the morphological function of the separated components; it is conducted using the Janus green live dyeing method, which is easy to operate and stable in performance. However, at high concentrations, sucrose has a high viscosity and high osmotic pressure, which can easily cause repeated shrinkage and mitochondrial expansion. Compared with sucrose, the price of commonly used density gradient media (including Percoll, Nycodenz and OptiPrep) is generally higher, but the morphology of the extracted mitochondria is generally complete. Percoll has a low diffusion constant, the gradient formed is very stable and it does not penetrate the biofilm; as such, it minimizes organelle rupture and is often used to isolate platelet mitochondria (12,34,35). Nycodenz is increasingly widely used owing to its high density, low viscosity and lack of effect on osmotic pressure (36-38). The yield of intact mitochondria is significantly higher in Nycodenz gradients containing sorbitol as an osmotic stabilizer instead of sucrose (37,38). As a dimer of Nycodenz, OptiPrep has the advantage of forming automatic gradients in a short period of time (39-42). Additionally, some researchers use streptavidin magnetic beads to separate Arabidopsis mitochondria. After the tissues are lysed, they are mixed with anti-mitochondrial outer membrane protein 22 (TOM22) magnetic beads and the mixed samples placed in the sorting column. Only mitochondria remain on the sorting column after washing, followed by elution, isolating the complete mitochondria in less than 30 min with a success rate, purity and integrity significantly higher than the density gradient centrifugation (43-47). Therefore, the magnetic bead method can be used to extract mitochondria in tissues with fewer mitochondria. As such, this approach will probably become increasingly common in mitochondrial extraction and purification (48-50). In conclusion, among the current mitochondrial extraction and purification methods, the magnetic bead method has the best effect on eliminating impurities such as microsomes and peroxisomes and the mitochondrial purity obtained by the differential centrifugation method is the lowest and the effect on eliminating these impurities is the worst.

3. Determination of mitochondrial morphology and structure

Mitochondria are organelles with a complex bi-membrane structure that regulate the entry and output of proteins, lipids, solutes and metabolite products and protect the cytoplasm from harmful mitochondrial products (51-53). Mitochondria can engulf abnormal mitochondria and remove excess harmful mitochondrial products to protect the body. This process is called mitophagy (54-56). Most mitochondria are spherical, rod-shaped, or tubular; however, mitochondrial morphology varies widely among tissues and cells depending on the energy requirements of cells and the location of mitochondria within the cell (53,57). For example, mitochondria are spherical at synaptic terminals, whereas they appear as highly elongated rods in axons. In senescent and functionally impaired cells, mitochondrial morphology is significantly different from that in normal cells and they can be irregularly shaped (53,58,59). Therefore, morphological changes can be used in the initial assessment of mitochondrial function.

After over 50 years since its development, electron microscopy (EM) has become the central tool for observing organelles in eukaryotic cells and is the gold standard for observing mitochondrial structure (60). It can reveal mitochondrial swelling, rupture and other abnormalities of damaged mitochondria. However, it cannot clearly distinguish mitochondria from other membranous structures and is occasionally confusing. In the 1980s, atomic force microscopy, as an emerging observation method, could study the surface structure and properties of substances by detecting the extremely weak interatomic interaction between the surface of the sample to be tested and a miniature force-sensitive element. Due to the characteristics of resolution and real-time imaging, changes such as the formation of mitochondrial swelling can also be observed under liquid conditions but are significantly affected by the probe; thus, the application range is small (61-64)

The recently developed AiryScan microscope (Zeiss AG) can acquire images at high speed with high sensitivity to effectively observe the kinetic processes of mitochondrial fission, fusion and autophagy (65-67). In addition, both wide-field fluorescence microscopy and high-resolution confocal laser scanning microscopy can be used for imaging analyses of morphological changes in mitochondria with higher specificity than that of EM, but the dynamic changes of the mitochondria cannot be observed (68-76).

In most cases, microscopy can be used to observe and analyze two-dimensional mitochondrial morphologies and quantities. However, although this method is suitable for analyzing adherent cells with flat morphology, it is not suitable for thicker cells (77-83). Three-dimensional confocal microscopy can be used to observe mitochondrial morphology by observing specifically labeled mitochondrial proteins at the 3D level (84-87). In addition, after labeling mitochondria with specific dyes, mitochondrial morphology can be visualized using a combination of immunofluorescent staining and computer images (58,88,89).

4. Determination of mitochondrial function

Determination of mitochondrial membrane potential

Mitochondrial membrane potential (MMP) refers to the negative potential difference between the two sides of the inner mitochondrial membrane. It is a sensitive indicator for evaluating mitochondrial function (90-93). It is closely associated with cellular homeostasis and is most commonly used to determine the metabolic state of mitochondria (93-98).

Fluorescent dye probes used for flow cytometry are now commonly used in MMP assays. For example, rhodamine 123, a specific stain developed in the 1980s, is widely used in flow cytometry and MMP assays. In normal cells, rhodamine 123 can selectively enter the mitochondrial matrix depending on MMP and can emit bright yellow-green fluorescence; when cells undergo apoptosis or necrosis, the mitochondrial membrane permeability transition pore (mPTP) is abnormally opened and MMP is unbalanced. Rhodamine 123 is released from mitochondria, resulting in a significant decrease in the yellow-green fluorescence intensity in mitochondria, which reflects the changes in MMP (50,99-102). 5,5',6,6'-Tetrachloro-1,1',3, 3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) has higher sensitivity than that of rhodamine 123. At low MMP levels, JC-1 exists as a monomer and produces green fluorescence; at high MMP levels, JC-1 aggregates in the mitochondrial matrix and forms polymeric JC-1. This can be used for qualitative and quantitative analyses of MMP by fluorescence microscopy or flow cytometry (50,96,101,103-108). Tetramethyl rhodamine methyl ester (TMRM) and tetramethyl rhodamine ethyl ester (TMRE), like JC-1, are specific dyes that have recently become common tools for measuring MMP (109-112). TMRM can be excited at 488 nm, showing red-orange fluorescence and its fluorescence intensity has a linear relationship with MMP. Compared to rhodamine 123 and JC-1, these two dyes are very soluble, have short loading times (15-20 min) and have extremely low cytotoxicity, requiring micromolar inhibition of mitochondrial function. With staining concentrations in the range of 0.5-30 nM (the concentration of JC-1 needs to be >0.1 µM), the accumulation in mitochondria is limited to the change of membrane potential and the sensitivity is extremely high; this is markedly suitable for quantitative analysis of mitochondrial membrane potential and quantitative flow cytometry (113-118). However, in quantitative flow cytometry studies, the data must be corrected for the signal of MitoTracker Green FM, a dye that is not dependent on mitochondrial membrane potential. It is worth noting that the above fluorescent probes for measuring MMP are applicable to most tissues and cells, including plant cells and bacteria.

Fluorescence resonance energy transfer (FRET) is a non-radiative energy transition that transfers energy from the excited state of the donor to the excited state of the acceptor through intermolecular electric dipole interactions (119,120). This process does not involve photons, so it is non-radiative. This analytical method has the advantages of rapidity, sensitivity and simplicity. Fluorescence resonance energy transfer molecular pairs (FRET Pairs) have been designed and synthesized to monitor MMPs (121). The FRET donor molecule (FixD) is constructed by attaching a benzyl chloride group to a fluorophore with green fluorescence emission. FixD can be attached to and fixed in mitochondria by sulfhydryl groups of mitochondrial proteins. The FRET acceptor (LA) is a mitochondrial membrane potential-dependent probe with green absorption and deep red fluorescence emission. When MMP is at a normal level, both FixD and LA target mitochondria. When FixD has an excitation wavelength of 405 nm, FRET occurs between FixD and LA, allowing green fluorescence to be detected but not deep red LA fluorescence emissions. When MMP is gradually reduced, LA will gradually fall off from mitochondria. While FixD is still fixed in mitochondria, the distance between the molecules gradually blocks the occurrence of FRET between FixD and LA molecules, allowing deep red fluorescence emission to be detected gradually. The decrease and the gradual increase of green fluorescence emission can be used to monitor the dynamic changes of MMPs (122), providing new ideas for the development of novel MMP fluorescent probes and real-time in situ studies of MMPs in living organisms, tissues and cells (123,124).

MMP varies greatly among sites on the mitochondrial membrane; therefore, accurate measurement of MMP requires further study (125). In recent years, low concentrations of a hemicyanine derivative (TPP-CY) have been used to monitor trace changes in MMP at the subcellular level during apoptosis with very high sensitivity (125). This approach is a potentially useful tool for evaluating cell health.

Determination of mitochondrial oxygen consumption

Among organelles, mitochondria consume the most oxygen in cells and this oxygen consumption often reflects mitochondrial function (126-128). In the heart, mitochondrial oxygen consumption can be measured to determine cardiac mitochondrial function, providing an indicator of cardiac function (129-131). In children, mitochondrial dysfunction causes mitochondrial heart disease with hypertrophic myocardial infarction as the primary symptom; however, the exact mechanism and etiology remain to be investigated (129,132).

Oxygen electrode polarography is a common method for determining mitochondrial oxygen consumption and refers to the incubation of mitochondria in an oxygen-consuming medium in a magnetically stirred incubator at 30°C. Briefly, rotenone is used to inhibit complex I in the electron transport chain, followed by the addition of succinate to measure mitochondrial state IV respiration (non-phosphorylating respiration). State III respiration is measured by incubating mitochondria in the presence of succinate and adenosine diphosphate. The respiratory control ratio (RCR) is the ratio of the state III respiration rate to state IV respiration rate, with a normal value of 3-10 (133-135). A low RCR indicates impaired mitochondrial ATP synthesis and mitochondrial dysfunction and a high RCR indicates vigorous cellular activity and accelerated metabolism (127,136,137).

In addition, the hippocampal analyzer can measure the changes in oxygen and pH levels through sensors and then automatically calculate the rate and detect the cellular oxygen consumption rate (OCR) and extracellular phosphorylation rate (ECAR) in real time to characterize the metabolic status of cells. Where OCR is caused by mitochondrial electron transfer, ECAR is derived from lactic acid fermentation (glycolytic acidification) and carbon dioxide produced by mitochondria (mitochondrial acidification) (138-140).

OCR is used to study mitochondrial oxidative phosphorylation function, with pMoles/min as the readout type (141). Generally, basal respiration in a normal state is measured first and then oligomycin is added to inhibit ATP synthase. This is a significant decrease in OCR, leaving only proton leakage (142). The oxygen consumption rate is caused by proton leakage and the reduced section is the oxygen consumption rate (ATP production) of oxidative phosphorylation. With the addition of the uncoupling agent FCCP, electron transport loses the constraints of the proton gradient and proceeds at a maximum rate (143). Therefore, the OCR increases sharply, reaching the maximum oxygen consumption (maximal respiration); the difference between this value and the basal respiration is termed the spare respiratory capacity. Finally, adding an electron transport inhibitor, such as antimycin A, completely inhibits electron transport and reduces the oxygen consumption rate to a minimum (144).

ECAR is often used to study metabolic conditions such as glycolysis, with mpH/min as the readout type (139,140,142). The basal value before adding glucose is non-catalytic acid production, such as mitochondrial acidification caused by carbon dioxide produced by mitochondrial respiration. Glucose is then added and the elevated value represents glycolysis. After the addition of oligomycin, the production of acid increases because oxidative phosphorylation is inhibited and the cells are forced to use lactic acid fermentation for energy. The value at this time is called glycolytic capacity and the difference from glycolysis is termed glycolytic reserve (140,142,143). Last added is 2-deoxyglucose, a competitive hexokinase inhibitor that can block glycolysis, so the curve should return to the basic value following its addition (144-146).

However, the direct measurement of glycolysis by ECAR is somewhat biased since the addition of glucose enhances glycolysis and oxidative phosphorylation. This will lead to increased mitochondrial acidification, causing the calculated amount of glycolysis to be high (147-149).

It is worth noting that during the measurement process of the hippocampal analyzer, the interference of phenol red should be avoided because it causes errors in the measurement results (141,150,151), but the specific reasons remain to be elucidated. In conclusion, the hippocampal analyzer can monitor OCR and ECAR to obtain multiple other parameters in a single analysis, including basal respiration, ATP-related respiration, maximal respiration, spare respiratory capacity and non-mitochondrial oxygen consumption, all of which can provide information on the mechanism of mitochondrial dysfunction (152,153).

Determination of mitochondrial Ca2+

Intracellular Ca2+ is primarily stored in organelles, such as the mitochondria and endoplasmic reticulum, and serves an important role in biological processes such as signal transduction, blood coagulation, transmembrane ion transport and cell division (154-156). Mitochondrial Ca2+ is a central regulator of oxidative phosphorylation and serves a key role in the control of ATP synthesis (157). A Ca2+ imbalance can cause abnormal mitochondrial function and even cell damage and death, leading to pathological changes and affecting organismal health (158,159). The accumulation of mitochondrial Ca2+ promotes ATP synthesis in mitochondria; conversely, decreased mitochondrial Ca2+ leads to a decrease in mitochondrial ATP. Impaired ATP synthesis further leads to a Ca2+ imbalance (157,159), which in turn leads to endocrine dysfunction and numerous diseases, such as mitochondrial diabetes mellitus (160-165).

Methods for the determination of mitochondrial Ca2+ include precipitation, electrochemical analysis, EDTA chelation titration, flame photometry and atomic absorption spectroscopy, among which electrochemical analysis is the most convenient (87,88,156,166-168). First developed in the 19th century, the electrochemical analysis applies electrochemical principles and techniques to a class of analytical methods that take advantage of the electrochemical properties of chemical cells in solution and their changes. It can be used for the detection of both organic and inorganic substances and is simple in operation. It can be both qualitative and quantitative, but is susceptible to interference by sodium, potassium, phosphate and sulfate. It is suitable for real-time detection and experiments with low optical sensitivity requirements (132,169). In addition, FRET can also detect Ca2+; cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP) are the most widely used FRET pairs in protein-protein interaction studies. The emission spectrum of CFP is similar to that of YFP. The absorption spectra of CFP overlap and when the distance between the two proteins is in the range of 5-10 nm, the fluorescence emitted by CFP can be absorbed by YFP and YFP is excited to emit yellow fluorescence. Whether the two proteins interact was determined by measuring the loss of CFP fluorescence intensity. The closer the two proteins are, the more fluorescence emitted by CFP is received by YFP and the less fluorescence is received by the detector. CFP and YFP are fused to calmodulin and calmodulin-binding peptide, respectively and expressed in the same cell (170-175). When the intracellular Ca2+ concentration is high, the combination of calmodulin and the calmodulin-binding peptide can induce FRET and the receptor protein YFP emits yellow fluorescence, so the cells appear yellow. When the intracellular Ca2+ concentration is low, FRET hardly occurs, so CFP is excited and emits green fluorescence during detection and the cells appear green (170,171,175). FRET can detect intracellular Ca2+, but cannot specifically detect mitochondrial Ca2+. A number of fluorescent probes have recently been used for the measurement of Ca2+ levels, including Quin-2AM, fluo-3AM, indo-1AM, Rhod-2, Fluo-4, Mag-fluo-4 and calcium-rhodamine 123 (rhodamine 123) (158,176-178). Quin-2AM, fluo-3AM, indo-1AM, Fluo-4 are cytosolic Ca2+ indicators. Mag-fluo-4 is an ER Ca2+ indicator. The rhodamine 123 complex assay is suitable for the determination of mitochondrial Ca2+ concentrations in various living cells owing to its simple operation and stable performance. It can be quantified by fluorescence spectrophotometry to detect aggregation in mitochondria and thereby to measure the Ca2+ content (179-184). At present, Fluo-3 is a widely used typical single-wavelength fluorescent indicator with an excitation wavelength in the visible light range (185,186). The maximum absorption peak and maximum emission wavelength are located at 506 and 526 nm, respectively. The fluorescence intensity of Fluo-3 combined with Ca2+ is ~40 times higher than that of free cells, thus avoiding the fluorescence interference of the cells themselves (185,187). As a long-wavelength indicator, Fluo-3 can be used in confocal laser imaging studies that can analyze the distribution of Ca2+ in individual intact living cells and distinguish mitochondrial Ca2+ from Ca2+ in other organelles within the cell; this method is suitable for mitochondrial Ca2+ in various living cells and is easy to operate, stable in performance and highly specific (155,187). However, the current mitochondrial Ca2+ fluorescent probes cannot distinguish mitochondrial Ca2+ from different cells.

Detection of mitochondrial permeability transition pores

mPTP is a class of protein complexes between the inner and outer mitochondrial membranes that permit the passage of substances with a molecular weight of <1.5 kDa and serve as the structural basis for transitions in mitochondrial permeability (188-191). Additionally, mPTP is very sensitive to changes in intracellular and extracellular ion concentrations and serves an important role in signal transduction systems. It is currently hypothesized that the abnormal opening of mPTP is closely associated with abnormal changes in Ca2+ concentrations, oxidative stress and mitochondrial DNA (mtDNA) mutations (154,188,189,192,193). By contrast, MMP and mitochondrial Ca2+ concentrations are the principal drivers of mPTP opening, resulting in the release of cytochrome c and other substances associated with cell death into the cytosol (191,192,194-197). This leads to mitochondrial swelling and reduced mitochondrial respiratory chain activity, which can cause various diseases, such as neurodegenerative diseases and cancers (190,198-200). Furthermore, studies have shown that PINK1 can inhibit mPTP opening by downregulating intracellular ROS levels, suggesting that mitochondrial autophagy serves a regulatory role in mPTP opening (191-193). Various methods have been developed for detecting mPTP, such as the patch-clamp, spectrophotometric and active substance labeling methods. The patch-clamp method is the earliest, originating in 1976 and can reflect ion channel activity by recording ion channel currents to evaluate mitochondrial function (188,189,201). As the magnification of AFM is as high as 1 billion times, the opening of mPTP can be directly observed, which can serve a guiding role in the abnormal opening of mPTP (202-205). Fully automated patch-clamp techniques have recently emerged; these are simple in operation and have greatly improved efficiency but are only applicable to the detection of cells in suspension. Compared to the active substance labeling and patch-clamp methods, spectrophotometry is simpler and more commonly used.

The calcein-cobalt fluorescent probe technique is an emerging technique for the detection of mPTP and is simple in operation and highly sensitive (Fig. 2). Calcein-AM (190,194, 198,206,207), in which the acetylmethoxy methyl ester (AM) group enhances the hydrophobicity of the stain for easy penetration of the living cell membrane, is used to fluorescently label living cells. Next, calcein-AM is cleaved by intracellular esterases to yield highly fluorescent and polar calcein (208-210). When cells are incubated with calcein and Co2+, both enter the cytoplasm; however, calcein is further captured by mitochondria (211,212). Calcein that accumulates in the mitochondria exhibits fluorescent staining, whereas calcein remaining in the cytoplasm or released from the mitochondria into the cytoplasm is rapidly quenched by Co2+ (213-219). Under normal physiological conditions, mPTP opens transiently and calcein that enters the cytoplasm from the mitochondria is rapidly quenched. In pathological states, such as calcium overload and oxidative stress, mPTP can appear to be continuously open and Co2+ in the cytoplasm can enter the mitochondria to quench the calcein fluorescence, resulting in a gradual decrease in fluorescence intensity in the mitochondria, thus indicating the degree of mPTP opening (195,196,220-222).

Determination of mitochondrial ATP

ATP is often considered the primary energy currency of cells and is primarily derived from the mitochondria (137,223-228). It serves major roles in material transport, energy conversion and information transfer. Mitochondria are sensitive to external environmental stimuli, such as hypoxia, oxidative stress, toxic substances and high glucose. Once mitochondria are damaged, ATP production decreases and free radical production increases, which affects a number of cellular processes and contributes to the development of a number of diseases, such as Parkinson's disease, cancer, cardiovascular disease and endocrine dysfunction (224-227). Therefore, ATP levels are a key indicator of the status of cellular energy metabolism and mitochondrial function.

Analyzing ATP levels requires freshly extracted mitochondria, as mitochondria must remain intact and in a coupled state (229). Several techniques are available to measure mitochondrial ATP levels, including chromatography, electrophoresis, high-performance liquid chromatography (HPLC) and enzymatic analysis (225,227,229-232). Chromatography and electrophoresis are chemical methods that were developed in the 18 and 19th centuries and have gradually improved. Classic liquid chromatography uses a large-diameter glass tube column and a difference in liquid levels at room temperature and atmospheric pressure to force the mobile phase (231,232). However, this technique has low column efficiency and is very time-consuming (often requiring several hours). HPLC was developed based on classic liquid chromatography following the introduction of gas chromatography theory in the late 1960s. The differences between HPLC and classic liquid chromatography include a faster analysis speed, smaller and more uniform particles as packing material and high column efficiency of the small particles. However, this causes high resistance and requires high pressure to force the mobile phase; therefore, this technique is also known as high-speed liquid chromatography (233-235). HPLC can be used to determine differences in cellular energy substances in different states, is easy to operate and has high sensitivity (233-236). The enzymatic method is based on spectrophotometry, where ADP production is assessed by measuring the absorbance of NAD+ in phosphoenolpyruvate (237-240). Fluorescence analysis techniques have been improved in recent years and are commonly used to determine mitochondrial ATP synthesis activity (241-244). For example, in the luciferin-luciferase luminescence method, luciferin is rapidly oxidized under the action of luciferase, producing green fluorescence and the amount of luminescence is linearly correlated with the level of ATP (245,246). This is a fast and accurate method; however, fluorescein is an amphiphilic molecule whose carboxyl group is charged at physiological pH and thus does not easily cross the cell membrane (244-246). A novel synthetic fluorescent probe called Mito-Rh can specifically identify ATP in mitochondria with high sensitivity and a detection range of 0.1-10 mM. In another method, the level of ATP can be determined directly by measuring the amount of inorganic phosphate based on the principle that ATP gives rise to ADP and inorganic phosphate (225). In addition, FRET can also be used to detect the level of ATP synthesis after labeling the ATP synthase subunit. When CFP and YFP are labeled on ATP synthase subunits, when the ATP synthase activity is enhanced, the interaction between the subunits is enhanced, the shortened distance between the subunits brings CFP and YFP closer to each other and FRET occurs and CFP excites YFP to emit yellow fluorescence. The lower the green fluorescence intensity received by the detector, the higher the ATP synthase activity and the higher the ATP level. When ATP synthase activity is low, the interaction between subunits is weakened, FRET hardly occurs and CFP is excited at this time and the cell emits green light.

In addition, a multi-color ATP indicator has appeared in recent years. Different from the previous indicators that can only specifically detect intracellular ATP, the multi-color ATP indicator is based on a single fluorescent protein indicator with red, green and blue colors (247-249). Alternatively, it can simultaneously detect ATP in different organelles in the same cell and simultaneously detect ATP dynamics in the mitochondria of mammalian, plant and even worm cells and will have an assured role in promoting energy metabolism research in the future (225,226).

Detection of mitochondrial respiratory chain complexes

The mitochondrial respiratory chain, with functions in energy production, the regulation of cell death and calcium metabolism (183,250-253), is located on the inner mitochondrial membrane and consists of five complexes. Mitochondrial respiratory chain complex I (NADH oxidase) and mitochondrial respiratory chain complex II (succinate dehydrogenase) are the major elements for electrons entering the mitochondrial electron transport chain (ETC). Complex I oxidizes NADH and transfers electrons to coenzyme Q (254-257). Complex II transfers electrons from succinate to coenzyme Q, a process that does not involve proton transport (258-260). Mitochondrial respiratory chain complex III (cytochrome c reductase) is an essential protein for mitochondrial oxidative phosphorylation, the gatekeeper of the mitochondrial respiratory chain and a major source of third reactive oxygen species. Complex III transfers electrons from coenzyme Q to cytochrome c while using the released energy to pump protons into the intermembrane space. The mitochondrial respiratory chain complex IV (cytochrome c oxidase) is the terminal electron acceptor of the mitochondrial electron transport chain. Complex IV transfers electrons from cytochrome c to oxygen, half the number of protons is synthesized into water and the other half is pumped into the intermembrane space. Mitochondrial respiratory chain complex V and the above four complexes complete oxidative phosphorylation to generate ATP, which is called ATP synthase, also known as F1F0-ATPase (254,260-265). The energy released by complex V through the electron transport chain during respiration or photosynthesis is first converted into a transmembrane proton (H+) gradient and the proton then flows along the proton gradient and passes through ATP synthase to enable ADP+Pi to synthesize ATP (266-269). It is also hypothesized that abnormalities in mitochondrial complexes are closely associated with mitochondrial encephalopathy, mitochondrial liver disease and mitochondrial nephropathy (265). It should be noted that the mitochondrial respiratory chain complex is closely related to the occurrence of tumors (251,270-272). Therefore, mitochondrial complex inhibitors may be used as a new treatment for tumors (252,253,260,273). Therefore, the accurate detection of mitochondrial complexes is essential and spectrophotometric assays remain the first-line technique for detecting the activity of mitochondrial respiratory chain complexes I-V (266,274,275).

Samples are generally selected from purified mitochondria and 4-40 µg of mitochondrial protein is required per respiratory chain complex assay (257,269,276-279). To compare the activity of mitochondrial respiratory chain complexes in different cells or tissues, the activity of citrate synthase in the Krebs cycle is measured simultaneously as a control and the reaction system is carried out at 30°C in a volume of 200 µl or 1 ml. The activity of complexes I and V is directly proportional to, and can be determined by measuring, the oxidation rate of NADH, which is measured as the decrease in absorbance at 340 nm (280). In the oxidation of succinate catalyzed by complex II, 2,6-dichlorophenolindophenol (DCPIP) is used as a dye and absorbance at 600 nm decreases as DCPIP decreases (259,281,282), which is used to measure the activity of complex II (283-287). The activity of complexes III and IV can be determined by measuring cytochrome activity (absorbance at 550 nm) (268,288-294). However, the spectrophotometric method is susceptible to external biochemical interference that can lead to changes in enzyme kinetics (chemicals in the liquid or gas phase react with the sample resulting in a change in the absorbance of the sample), which can have serious effects on the sensitivity and accuracy of the assay (255,258,280,295-298). In addition, western blotting can directly reflect the expression level of respiratory chain complexes I-V in the band by using the specific antibody reaction of the complex, which has been widely used in experiments related to mitochondrial research (274,296,297). However, the protein expression level and protein activity are occasionally not correlated and spectrophotometry is still the preferred method for detecting mitochondrial respiratory chain complexes. In recent years, great progress has been made in the non-invasive measurement of mitochondrial complexes using near-infrared spectroscopy. This method is similar to spectrophotometry in principle but is less affected by the external environment (265-268). The fundamental reason why near-infrared light can achieve non-invasive optical measurement is that in the near-infrared light region of 600-900 nm, biological tissue is relatively transparent because the absorption of water and hemoglobin in this wavelength region is very small. As an 'optical window', some studies have used it to detect the activity of complex IV to judge the severity of depression. Myoglobin is essential for oxygen metabolism in muscle tissue, including a group of blood cells similar to hemoglobin. The most important of which is complex IV, which has been used to detect the activity of complex IV to judge the severity of depression (299,300). However, due to the large amount of samples required for near-infrared spectroscopy and different instrument models, it has severe limitations and has not been widely used (183,250-253).

Mitochondrial respiratory chain function can also be determined by RCR, which reflects both mitochondrial integrity and mitochondrial oxidative respiratory chain function (256,265,267,301).

Measurement of ROS

As the central organelle for cellular oxidative phosphorylation, mitochondria are the principal site of ROS production (3,302-305). Under physiological conditions, the intracellular antioxidant defense system is in equilibrium with oxygen radicals. The levels of intracellular ROS, including superoxide radicals, hydrogen peroxide and its downstream products (peroxides and hydroxyl radicals), are maintained at low physiological ranges. Under pathological conditions, the balance between the intracellular antioxidant system and oxygen radicals is disrupted. When intracellular ROS levels are too high, mitochondrial structure and function are impaired and cytochrome c is released through mPTP, resulting in damage to mitochondrial enzymes, lipids and nucleic acids as well as oxidative stress (303,306-310). ROS can also attack mitochondrial DNA (mtDNA) to produce oxidative damage, resulting in reduced mitochondrial ATP synthesis and MMP damage. Therefore, the functional status of mitochondria can be determined by measuring ROS levels (311-313).

Common methods for detecting ROS include the chemical reaction method, selective electrode method, spectrophotometry and direct detection by kits. ROS shows high reactivity and can react with different compounds to produce various products, which can be analyzed quantitatively or qualitatively. The chemical reaction method is characterized by high sensitivity, low cost and simple operation; however, it has poor specificity and measurement results are easily affected by some redox reactions or enzyme-catalyzed reactions. Tetranitromethane, nitrotetrazolium blue chloride (NBT), cytochrome c, epinephrine and reduced coenzyme I are commonly used for spectrophotometric methods; these react with superoxide anion radicals to produce ferrous cytochromes with a specific absorbance (detectable at a wavelength of 550 nm), which can be used to directly measure ROS levels (307,314-317). The NBT assay is highly sensitive and is commonly used for the histochemical localization of oxygen radicals; however, it is difficult to measure dynamic changes in oxygen radicals in cells or aqueous systems. Cytochrome c has oxidative activity and can be used to detect the production of oxygen radicals. However, cytochrome c is easily reduced by other reducing agents and is therefore limited for the accurate localization of oxygen radicals. In the last decade, a number of ROS kits have been developed to detect intracellular or mitochondrial ROS (mtROS) levels directly. Intracellular ROS are usually measured using the fluorescent probe DCHF-DA, which is non-fluorescent and can freely cross the cell membrane. After DCHF-DA enters cells, it is hydrolyzed by intracellular esterases to generate DCHF, which cannot enter or exit the cell membrane, thus allowing the probe to easily label the cell. In the presence of ROS, DCHF is oxidized to produce the fluorescent substance DCF, whose fluorescence intensity is directly proportional to intracellular ROS levels. mtROS is usually measured using the fluorescent probe MitoSOX, which is highly specific to mitochondrial ROS and is characterized by simple operation, low background signals, wide linear range and high detection efficiency; however, it requires the immediate imaging of assay results and protection from light to prevent fluorescence quenching. Prior to the widespread use of kits, ROS levels were indirectly measured by detecting products of oxidative damage. Levels of malondialdehyde (MDA) reflect the degree of lipid peroxidation in the body and can be measured using the thiobarbituric acid (TBA) chemical colorimetric method. Condensation under acidic conditions generates the MDA-TBA complex, a red product with a maximum absorption peak at 535 nm, which can be used to indirectly determine the MDA content by spectrophotometry, indicating ROS levels. However, this technique has poor sensitivity and is prone to contamination. Fluorescent protein-based ROS detection methods are designed by combining fluorescent proteins and prokaryotic redox-sensitive proteins (318,319). The recombinant proteins are introduced into cells via plasmids or adenoviruses and target organelles to detect intracellular redox status (320,321). Redox-dependent fluorescence spectral changes of recombinant proteins are achieved through structural changes of disulfide bonds and part of the backbone under oxidative conditions (319,321).

Electron spin resonance (ESR) technology has emerged in recent years. Also known as electron paramagnetic resonance (EPR), its principle is similar to nuclear magnetic resonance (322-325). The sample is controlled in a fixed frequency microwave and the applied magnetic field is then changed so that the electron energy level difference is the same as the microwave energy (326,327). Unpaired electrons can move between the two energy levels and the net absorption energy of the microwave can be measured to obtain the ESR spectrum. Due to the high reactivity and short lifespan of ROS, the ESR signal is not easy to detect directly. The combination of ESR and spin traps can make up for this defect. The spin-electron trapping agent reacts with free radicals to generate relatively stable free radical addition products that are easily detected by ESR, which is then determined by ESR technology. This powerful and reliable technique can unambiguously measure the presence of free radicals in biological samples. ROS is the most direct and effective method for detecting free radicals and is widely used in physics, chemistry and biomedicine (328-331).

Detection of mtDNA

Human mitochondria carry a small circular double-stranded genome of 16569 bp known as mtDNA, which encodes mitochondrial 16S and 12S ribosomal RNA, 22 mitochondrial tRNA molecules and 13 respiratory chain proteins. Each organism contains only one type of mtDNA and mutations such as the conversion, inversion, insertion, or deletion of one or several bases of mtDNA, resulting in more than one type of mtDNA within an individual, are referred to as mtDNA heterogeneity (332-335). Owing to the lack of protective histones and effective DNA repair systems, the mutation frequency of mtDNA is ~10 times higher than that of nuclear DNA (336-339). Moreover, mutated mtDNA gradually accumulates and can cause irreversible damage to the nervous, cardiovascular, respiratory and reproductive systems after reaching a certain threshold (60-80%). In addition to these diseases, studies have also shown that mtDNA mutations are closely associated with the development of infertility (308,339-342). mtDNA dysfunction can be both quantitative (e.g., mtDNA copy number variation and deletions) and qualitative (e.g., strand breaks, point mutations and oxidative damage) (343-345).

mtDNA can be released from the cell as circulating free mitochondrial DNA (CCF-mtDNA) via extracellular vesicles (EVs) (346,347). CCF-mtDNA can serve as a damage-associated molecular pattern leading to the activation of inflammatory pathways, a process closely associated with TLR9. Numerous reports have shown that elevated levels of CCF-mtDNA are associated with various TLR9-dependent pathologies, such as rheumatoid arthritis, atherosclerosis, hypertension, acute liver injury and nonalcoholic steatohepatitis (48,348).

mtDNA damage can be detected using PCR, fluorescence in situ hybridization (FISH), DNA sequencing technology and the probe method, among others. The principle of DNA sequencing is to use DNA polymerase to extend the primers bound to the template of the undetermined sequence until a chain-terminating nucleotide is incorporated. Termination of replication and detection with isotopic labeling is the gold standard for detecting heterogeneity, but speed is limited when working on large-scale projects. The speed of large-scale projects was not guaranteed until the advent of high-throughput sequencing. PCR, as a molecular biology technology that emerged in the 1980s, is a method for enzymatically synthesizing and amplifying specific nucleic acid fragments in vitro based on the semi-conservative replication mechanism of DNA. This can purposefully amplify target regions and is especially suitable for enriching small-scale genomes such as mtDNA (349-353). However, mtDNA is present in primer-binding regions, but accuracy is not sufficient due to heterogeneity. Over time, reverse transcription-quantitative (RT-q) PCR is able to monitor the number of amplified DNA molecules in real time, facilitating the determination of mtDNA in individual cells, along with the copy number and other impairments (deletions) (350-352). As a contemporaneous product of PCR, FISH is also a classic specific detection method. It uses fluorescently labeled specific nucleic acid probes to hybridize with corresponding target DNA or RNA molecules in cells. Fluorescent signaling with relatively poor specificity and insufficient hybridization compared to PCR is not the method of choice for the detection of mtDNA (149,354-362). Moreover, after the mitochondria are separated from cells or tissues, the DNA in the remaining material is extracted (kits can be used) and the DNA of the sample can be sequenced. qPCR or chromatin immunoprecipitation (ChIP) experimental methods can be used to detect the level of CCF-mtDNA, among which ChIP is often used to verify the binding of mtDNA to downstream signaling pathways, such as TLR9 inflammatory pathway or cGAS signaling pathway (335,363-371). As a DNA sensor in the cytoplasm, cGAS can recognize CCF-mtDNA and then catalyze the formation of the second messenger cGAMP (2'3'-cGAMP) to activate the interferon-stimulated gene-dependent signaling pathway. In addition, CCF-mtDNA containing unmethylated DNA (CpG DNA) fragments can be recognized by TLR9, causing TLR9 dimerization and activation of MyD88-mediated inflammatory pathway.

Unrepaired depurinated/depyrimidinated sites (AP sites) in mtDNA lead to the misbinding of nucleotides, which can have serious downstream effects (372-374). Therefore, the rapid and accurate quantification of AP sites in mtDNA is crucial for the real-time assessment of mtDNA oxidative damage. Researchers have used a specific fluorescent probe (BTBM-CN2) for the real-time detection of mtDNA (375-378). At ~20 sec after contact with AP sites, red fluorescence is detectable at 598 nm and after ~100 sec, green fluorescence is detectable at 480 nm. More AP sites result in green fluorescence with greater intensity and duration and the degree of mtDNA damage can be quantified based on the time of appearance and intensity of fluorescence at 480 nm. Doxorubicin (Dox), a common anticancer drug, not only causes damage to the nuclear DNA of cells but can also be rapidly inserted into the mtDNA of living cells, causing the aggregation of mtDNA nucleoids and changing the distribution of nuclear proteins (375-382). Therefore, after Dox induces mtDNA damage, morphological changes of mtDNA can be tracked in real time using the two-photon fluorescent probe CNQ, which emits red fluorescence and is localized to mtDNA. When incubated with Dox, dynamic changes in mtDNA can be observed, providing a new method for studying mtDNA damage in real time (383,384).

5. Treatment of mitochondrial diseases

In addition to primary mitochondrial disease caused by mtDNA damage, mitochondrial dysfunction occurs in a number of infectious and non-infectious diseases (262,385,386), such as inflammation, neurodegeneration, diabetes, obesity and cardiovascular disease and several therapies targeting mitochondria have been developed (Table II). Mitochondrial transplantation and mitochondrial replacement can fundamentally address the inadequate energy supply in pathological states and have been applied in clinical settings for the treatment of pediatric congenital heart disease (385).

Table II

Treatment of mitochondrial diseases.

Table II

Treatment of mitochondrial diseases.

Author, yearMitochondrial diseasesTreatment methodRepresentative interventionMechanismEffect on mitochondriaApplication status(Refs.)
Feng et al, 2019Primary mitochondrial diseaseEdit mtDNAAAV, CRISPR-Cas9Reduce mtDNA damageProtectionPre-clinical(379-415)
Dabravolski et al, 2022
Hamel et al, 2021
Karshovska et al, 2020
Gao et al, 2019
Grady et al, 2018
Bozi et al, 2020
Jing et al, 2019
Amore et al, 2021
Chen and Bhatti, 2021
Mejia-Vergara et al, 2020
Newman et al, 2021
Stenton et al, 2021
Wang et al, 2021
Yu-Wai-Man et al, 2020
Heighton et al, 2019
Wu et al, 2019
Del Monte et al, 2021
Di Mambro et al, 2021
Di Nora et al, 2019
Nguyen et al, 2019
Ashton et al, 2018
Bonora et al, 2019
Ni et al, 2018MSC-EVs
Porporato et al, 2018
Qi et al, 2019
Ramachandra et al, 2020
Soukas et al, 2019
Bonora et al, 2021
D'Angelo et al, 2020
Hirano et al, 2021
Kripps et al, 2020
Parés et al, 2021
Jackson et al, 2020
Jiang and Shen, 2022
Mok et al, 2020
Ng et al, 2021
Fang et al, 2019
Gong et al, 2021
González et al, 2021
Gu et al, 2017
Feng et al, 2019Pediatric congenital heart diseaseMitochondrial renewalMitochondrial transplantationMitochondrial numbersProtectionClinical evaluation(379)
Feng et al, 2019Mitochondrial replacement
Li et al, 2017 Bhatti et al, 2017Metabolic disease, neurodegenerative disorderVitamin E(55,168, 417-419)
Li et al, 2017Ubiquinone
Bhatti et al, 2017
Li et al, 2017 N-acetylcysteineOxidative stressProtectionHave been
Bhatti et al, 2017approved
Li et al, 2017Glutathione
Bhatti et al, 2017
Li et al, 2017Melatonin
Bhatti et al, 2017
Gong et al, 2021DrugsTetracyclines,
González et al, 2021Actinomycins
Gu et al, 2017
He et al, 2019
Gong et al, 2021Creatine, Ursodeoxycholic acid
González et al, 2021
Gu et al, 2017
Russell et al, 2020 Saeb-Parsy et al, 2021Heart and kidney disease, sepsis, diabetesSS-31Remove reactive oxygen species,ProtectionClinical evaluation(437-451)
Kelly and Pearce, 2020protect and restore mitochondrial structure
Rahman and Rahman, 2018
Tabish and Narayan, 2021
Yuan et al, 2021
Ballarò et al, 2021
Bhatti et al, 2021mitoTEMPO
Deng et al, 2021
Le Gal et al, 2021
Bhatti et al, 2021Pre-clinical
Grosser et al, 2021
He et al, 2022
He et al, 2021
He et al, 2021
Labarta et al, 2019ResveratrolMitochondrial biogenesisProtectionHave been approved(54,395, 396,399, 400,435, 465-471)
Wu et al, 2019
Del Monte et al, 2021
Nguyen et al, 2019ATP deficiency
Ashton et al, 2018AICARPre-clinical
Roth et al, 2020
Del Monte et al, 2021EpicatechinHave been approved
Nguyen et al, 2019
Gabandé-Rodríguez et al, 2019
Cho et al, 2020
Liu et al, 2021
Deng et al, 2020RTA-408Pre-clinical
Gao et al, 2020
Andrieux et al, 2021
Zeng et al, 2021
Heighton et al, 2019CancersNanomaterialsTPPMitochondrial membrane potentialProtectionPre-clinical((394-(400)
Wu et al, 2019(420-(436)
Del Monte et al, 2021
Di Mambro et al, 2021
Di Nora et al, 2019
Nguyen et al, 2019
Ashton et al, 2018
He et al, 2019MPPs
He et al, 2020
He et al, 2020
Zhao et al, 2021
Macdonald et al, 2018
Tan et al, 2013
Lee et al, 2019
Wallace, 2018
Strobbe and Campanella, 2018
Wang et al, 2018
Kim et al, 2017Graphene
Lleonart et al, 2017
Tian et al, 2021
Kim et al, 2017
Chen et al, 2017
Jung et al, 2017
Roth et al, 2020
Nash et al, 2021

[i] mtDNA, mitochondrial DNA; MSC-EVs, mesenchymal stem cell-derived extracellular vesicles; TPP, triphenylphosphine; MMP, mitochondrial membrane potential.

Leber hereditary optic neuropathy (LHON), the most common primary mitochondrial disease, is a maternally-inherited bilateral-blinding optic neuropathy mainly caused by mtDNA mutations, including m.3460G>A (MT-ND1), m.11778G>A (MT-ND4) and m.14484T>C (MT-ND6), of which m.11778G>A is the most common mutation (387,388). These mutations can affect the mitochondrial respiratory chain complex I of retinal ganglion cells, impair mitochondrial function and increase the production of reactive oxygen species, leading to apoptosis and optic nerve degeneration and atrophy, which further leads to rapidly progressive loss of binocular vision (389-391). Treatment of LHON is mostly based on ectopic expression, that is, intravitreal injection of adeno-associated viral vectors with mitochondrial targeting sequences and then guiding the translated protein into mitochondria to restore mitochondrial function, which has been successfully and safely applied to cell models. Transplant into an inducible LHON animal model that preserves retinal ganglion cells and visual function (392,393).

The mitochondrial diseases associated with mtDNA deletion mainly include chronic progressive external ophthalmoplegia (CPEO), Kearns-Sayre syndrome (KSS) and Pearson syndrome. CPEO is mostly associated with m.3243A>G(MT-TL1) deletion, which manifests as progressive paralysis of the ocular muscles, resulting in ocular movement disorders and ptosis, which usually appear in late childhood or early adulthood (394,395). KSS is a more severe syndrome than CPEO and is mostly associated with m.8993T>G (APT6) deletion. Its main clinical manifestations are progressive external ophthalmoplegia and retinitis pigmentosa, usually occurring before the age of 20 (396-399). Other symptoms may include mild skeletal muscle weakness, hearing loss, cognitive impaired cognitive function and diabetes. Pearson's syndrome is a syndrome caused by sideroblastic anemia and pancreatic exocrine insufficiency. There are very few cases (~100 cases worldwide) that may be related to the deletion of ATPase 6 and 8. Most patients die during infancy; however, a minority of patients who survive into adulthood tend to develop symptoms of KSS syndrome. Due to the double-membrane structure of mitochondria and the inability of foreign nucleic acids to recombine on endogenous mtDNA (168,400,401), there is currently no effective method to directly import nucleic acids into mitochondria and the localization of proteins to mitochondria is a routine practice in the treatment of mitochondrial diseases. In principle, expression of mitochondrial-targeted DNases that specifically recognize mutated sequences can remove mutated mtDNA, or at least reduce its abundance in a heterogeneous background. Restriction endonucleases, zinc finger nucleases and transcription activator-like effector nucleases have been tested and proven effective; these specific enzymes can be used to eliminate aberrant mtDNA and thereby reduce the rate of aberrant mtDNA in cells (402-406).

In addition, mitochondrial neurogastrointestinal encephalomyopathy, a rare mitochondrial disease, is often associated with TYMP gene mutations, manifesting as splanchnic neuropathy and marked motor impairment, often combined with CPEO, sensorimotor polyneuropathy and white matter encephalopathy (407-409). With advances in gene editing technology, CRISPR/Cas9 has been proposed for the treatment of mitochondrial diseases, aiming to eliminate abnormal mtDNA sequences through the principles of bacterial immunology (410,411).

To treat primary mitochondrial diseases, gene therapy based on ectopic expression is still the first choice; however, the application of viral vectors in live animals to correct any gene mutation still has the following significant problems: High cost (390,412-415), carcinogenicity and immunogenicity. Non-viral vector-mediated in situ mitochondrial gene therapy may be a promising approach to overcome the bottleneck of existing gene therapy LHON, such as liposome-based nanoparticles, which require further investigation (416-421).

Mesenchymal stem cell-derived EVs are a promising nanotherapeutic strategy to effectively attenuate mitochondrial damage and the inflammatory response by promoting mitochondrial transcription factor A expression and preventing mtDNA damage and leakage from target cells (422).

Oxidative stress caused by mitochondrial dysfunction is one of the etiologies of metabolic disease and is a potential target for the treatment of metabolic and neurodegenerative disorders (55,168,423-426). A number of antioxidants, such as vitamin E, ubiquinone, N-acetylcysteine, glutathione and melatonin, can effectively scavenge mitochondrial ROS and regulate redox processes, thus alleviating or curing disease. Antibiotics (e.g., tetracyclines and actinomycins), drugs (e.g., creatine and ursodeoxycholic acid) and exercise can significantly improve oxidative stress and balance mitochondrial fission and fusion, thus increasing the number of mitochondria, contributing to the treatment of cancer (400-406,426-442). SS31 and mitoTEMPO are novel mitochondrial-targeted antioxidants that have a scavenging effect on ROS (443-446). In addition, SS31 accumulates in the mitochondrial membrane to protect and restore the mitochondrial structure without affecting healthy mitochondria (162,447-453). Thus, SS31 and mitoTEMPO have protective effects on a variety of diseases, including heart and kidney-related diseases, as well as sepsis and diabetes, which have been demonstrated in a variety of animal models (454-457). The use of nanomaterials for mitochondrial targeting therapy has become a recent focus of research. Nanomaterials are materials with at least one of three spatial dimensions at the nanometer scale (1-100 nm). They are a new generation of materials composed of nanoparticles with sizes between atoms, molecules and macroscopic systems and are widely used in the medical field owing to their large specific surface area and excellent biocompatibility. Ideally, medical nanomaterials should remain quiescent in normal tissues but accumulate precisely and act in mitochondria under pathophysiological conditions (404,458,459). Delocalized lipophilic cations (DLCs), such as triphenylphosphine (TPP) and mitochondria-penetrating peptides (MPPs), serve a major role in mitochondria-targeted therapies. DLCs can accumulate specifically in the mitochondria of tumor cells and increase their MMP, leading to altered mitochondrial membrane permeability and inducing apoptosis (56,130,400,403,428,458-470). Studies have shown that graphene has a large specific surface area, good targeting and high biocompatibility, making it a promising nanodelivery system (441,471-473). Mitochondrial biogenesis is driven by PCG-1α, which can increase the number of mitochondria in the cell and thus meet the evolving energy demands of the cell, alleviating ATP deficiency in patients with mitochondrial diseases. Promoting mitochondrial biogenesis is also an important component of mitochondrial therapeutics (474). Resveratrol, 5-aminoimidazole-4-carboxamide riboside, epicatechin and RTA-408 have significant pro-mitochondrial biogenesis effects; the treatment of mice with these drugs enhances the expression of mitochondrial electron transport chain proteins and mitochondrial transcription factors and increases the abundance of mitochondrial cristae (54,401,402,405,406,441, 471-478).

6. Summary and outlook

As the powerhouses of the cell, mitochondria are at the center of cellular oxidative phosphorylation and are critical for growth and development as well as the development of a number of diseases. Mitochondrial abnormalities can cause disturbances in the intracellular environment and can lead to a variety of diseases, such as mitochondrial heart disease, mitochondrial encephalopathy, mitochondrial myopathy and even various pathologies of the reproductive and respiratory systems. Therefore, the accurate detection of mitochondrial abnormalities is essential for clinical guidance.

Since the beginning of the last century, a number of methods for mitochondrial research have been developed (Fig. 3), from the discovery of mitochondria as intracellular granular structures to the observation of mitochondrial microstructures via EM and the use of fluorescent probes to detect physiological indicators within mitochondria. The application of these methods has provided theoretical foundations for the detection and treatment of mitochondrial diseases. Accordingly, the treatment of mitochondrial diseases has gradually evolved from drug-based therapy to multidisciplinary combination therapies, such as the use of nanomaterials to precisely transport therapeutic drugs into mitochondria for targeted drug delivery, substantially improving therapeutic efficiency. However, the methods by which therapeutic efficacy is achieved still warrant investigation. The combined application of biomedicine and material science may be a promising means of detection and treatment. Notably, the specific molecular mechanism underlying the pathogenesis of the mitochondrial disease remains unclear. Current monitoring and treatment strategies cannot completely cure mitochondrial disease but only alleviate symptoms or slow disease progression. Therefore, methods for detection and treatment that are specific to the molecular mechanisms are needed. Using multi-omics and artificial intelligence, artificial mitochondrial models can be established through molecular co-assembly technology and mitochondria-targeted drugs can be screened to conduct in-depth discussions on abnormal mitochondria, which may elucidate the pathogenesis of mitochondrial diseases at the molecular level and provide new treatments for mitochondrial diseases.

Availability of data and materials

Data sharing is not applicable to this article, as no data sets were generated or analyzed during the current study.

Authors' contributions

YY wrote the first draft of this review. HS provided valuable comments on this first draft. Both authors read and approved the final manuscript.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Acknowledgments

Not applicable.

Funding

The present study was supported by the Foundation of Liaoning Education Department (grant no. JCZR2020014), the Liaoning Province Key R&D Program (grant no. 2020JH2/10300141) and the 345 Talent Project of Shengjing Hospital.

References

1 

Akbari M, Kirkwood TBL and Bohr VA: Mitochondria in the signaling pathways that control longevity and health span. Ageing Res Rev. 54:1009402019. View Article : Google Scholar : PubMed/NCBI

2 

Bock FJ and Tait SWG: Mitochondria as multifaceted regulators of cell death. Nat Rev Mol Cell Biol. 21:85–100. 2020. View Article : Google Scholar

3 

Chakrabarty RP and Chandel NS: Mitochondria as signaling organelles control mammalian stem cell fate. Cell Stem Cell. 28:394–408. 2021. View Article : Google Scholar : PubMed/NCBI

4 

Hood DA, Memme JM, Oliveira AN and Triolo M: Maintenance of skeletal muscle mitochondria in health, exercise, and aging. Annu Rev Physiol. 81:19–41. 2019. View Article : Google Scholar

5 

Li L, Conradson DM, Bharat V, Kim MJ, Hsieh CH, Minhas PS, Papakyrikos AM, Durairaj AS, Ludlam A, Andreasson KI, et al: A mitochondrial membrane-bridging machinery mediates signal transduction of intramitochondrial oxidation. Nat Metab. 3:1242–1258. 2021. View Article : Google Scholar : PubMed/NCBI

6 

Martínez-Reyes I and Chandel NS: Mitochondrial TCA cycle metabolites control physiology and disease. Nat Commun. 11:1022020. View Article : Google Scholar : PubMed/NCBI

7 

Kim Hong HT, Bich Phuong TT, Thu Thuy NT, Wheatley MD and Cushman JC: Simultaneous chloroplast, mitochondria isolation and mitochondrial protein preparation for two-dimensional electrophoresis analysis of ice plant leaves under well watered and water-deficit stressed treatments. Protein Expr Purif. 155:86–94. 2019. View Article : Google Scholar

8 

Boussardon C and Keech O: Cell type-specific isolation of mitochondria in Arabidopsis. Methods Mol Biol. 2363:13–23. 2022. View Article : Google Scholar

9 

Elekofehinti OO, Kamdem JP, Saliu TP, Famusiwa CD, Boligon A and Teixeira Rocha JB: Improvement of mitochondrial function by Tapinanthus globifer (A.Rich.) Tiegh. Against hepatotoxic agent in isolated rat's liver mitochondria. J Ethnopharmacol. 242:1120262019. View Article : Google Scholar : PubMed/NCBI

10 

Gäbelein CG, Feng Q, Sarajlic E, Zambelli T, Guillaume-Gentil O, Kornmann B and Vorholt JA: Mitochondria transplantation between living cells. PLoS Biol. 20:e30015762022. View Article : Google Scholar : PubMed/NCBI

11 

Lee D, Lee YH, Lee KH, Lee BS, Alishir A, Ko YJ, Kang KS and Kim KH: Aviculin isolated from lespedeza cuneata induce apoptosis in breast cancer cells through mitochondria-mediated caspase activation pathway. Molecules. 25:17082020. View Article : Google Scholar :

12 

Léger JL, Jougleux JL, Savadogo F, Pichaud N and Boudreau LH: Rapid isolation and purification of functional platelet mitochondria using a discontinuous percoll gradient. Platelets. 31:258–264. 2020. View Article : Google Scholar

13 

Léger JL, Pichaud N and Boudreau LH: Purification of functional platelet mitochondria using a discontinuous percoll gradient. Methods Mol Biol. 2276:57–66. 2021. View Article : Google Scholar : PubMed/NCBI

14 

Liao PC, Bergamini C, Fato R, Pon LA and Pallotti F: Isolation of mitochondria from cells and tissues. Methods Cell Biol. 155:3–31. 2020. View Article : Google Scholar : PubMed/NCBI

15 

Lin YT, Chen ST, Chang JC, Teoh RJ, Liu CS and Wang GJ: Green extraction of healthy and additive free mitochondria with a conventional centrifuge. Lab Chip. 19:3862–3869. 2019. View Article : Google Scholar : PubMed/NCBI

16 

Long Q, Huang L, Huang K and Yang Q: Assessing mitochondrial bioenergetics in isolated mitochondria from mouse heart tissues using oroboros 2k-oxygraph. Methods Mol Biol. 1966:237–246. 2019. View Article : Google Scholar : PubMed/NCBI

17 

Rahman MH, Xiao Q, Zhao S, Wei AC and Ho YP: Extraction of functional mitochondria based on membrane stiffness. Methods Mol Biol. 2276:343–355. 2021. View Article : Google Scholar : PubMed/NCBI

18 

Ramezani M, Samiei F and Pourahmad J: Anti-glioma effect of pseudosynanceia melanostigma venom on isolated mitochondria from glioblastoma cells. Asian Pac J Cancer Prev. 22:2295–2302. 2021. View Article : Google Scholar : PubMed/NCBI

19 

Ruzzenente B and Metodiev MD: Linear density sucrose gradients to study mitoribosomal biogenesis in tissue-specific knockout mice. Methods Mol Biol. 2224:47–60. 2021. View Article : Google Scholar : PubMed/NCBI

20 

Yang J, Cao L, Li Y, Liu H, Zhang M, Ma H, Wang B, Yuan X and Liu Q: Gracillin isolated from reineckia carnea induces apoptosis of A549 cells via the mitochondrial pathway. Drug Des Devel Ther. 15:233–243. 2021. View Article : Google Scholar :

21 

Chandra K, Kumar V, Werner SE and Odom TW: Separation of stabilized MOPS gold nanostars by density gradient centrifugation. ACS Omega. 2:4878–4884. 2017. View Article : Google Scholar : PubMed/NCBI

22 

Chen BY, Sung CW, Chen C, Cheng CM, Lin DP, Huang CT and Hsu MY: Advances in exosomes technology. Clin Chim Acta. 493:14–19. 2019. View Article : Google Scholar : PubMed/NCBI

23 

Écija-Arenas Á, Román-Pizarro V and Fernández-Romero JM: Luminescence continuous flow system for monitoring the efficiency of hybrid liposomes separation using multiphase density gradient centrifugation. Talanta. 222:1215322021. View Article : Google Scholar

24 

Hu P, Fabyanic E, Kwon DY, Tang S, Zhou Z and Wu H: Dissecting cell-type composition and activity-dependent transcriptional state in mammalian brains by massively parallel single-nucleus RNA-Seq. Mol Cell. 68:1006–1015.e7. 2017. View Article : Google Scholar : PubMed/NCBI

25 

Jerri HA, Sheehan WP, Snyder CE and Velegol D: Prolonging density gradient stability. Langmuir. 26:4725–4731. 2010. View Article : Google Scholar

26 

Johnson ME, Montoro Bustos AR and Winchester MR: Practical utilization of spICP-MS to study sucrose density gradient centrifugation for the separation of nanoparticles. Anal Bioanal Chem. 408:7629–7640. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Pužar Dominkuš P, Stenovec M, Sitar S, Lasič E, Zorec R, Plemenitaš A, Žagar E, Kreft M and Lenassi M: PKH26 labeling of extracellular vesicles: Characterization and cellular internalization of contaminating PKH26 nanoparticles. Biochim Biophys Acta Biomembr. 1860:1350–1361. 2018. View Article : Google Scholar

28 

Wang J, Shen T, Huang X, Kumar GR, Chen X, Zeng Z, Zhang R, Chen R, Li T, Zhang T, et al: Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound. J Hepatol. 65:700–710. 2016. View Article : Google Scholar : PubMed/NCBI

29 

Sugiura A, Nagashima S, Tokuyama T, Amo T, Matsuki Y, Ishido S, Kudo Y, McBride HM, Fukuda T, Matsushita N, et al: MITOL regulates endoplasmic reticulum-mitochondria contacts via Mitofusin2. Mol Cell. 51:20–34. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Xiong B, Cheng J, Qiao Y, Zhou R, He Y and Yeung ES: Separation of nanorods by density gradient centrifugation. J Chromatogr A. 1218:3823–3829. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Zheng X, Xu K, Zhou B, Chen T, Huang Y, Li Q, Wen F, Ge W, Wang J, Yu S, et al: A circulating extracellular vesicles-based novel screening tool for colorectal cancer revealed by shotgun and data-independent acquisition mass spectrometry. J Extracell Vesicles. 9:17502022020. View Article : Google Scholar : PubMed/NCBI

32 

Zhu J, Liu B, Wang Z, Wang D, Ni H, Zhang L and Wang Y: Exosomes from nicotine-stimulated macrophages accelerate atherosclerosis through miR-21-3p/PTEN-mediated VSMC migration and proliferation. Theranostics. 9:6901–6919. 2019. View Article : Google Scholar : PubMed/NCBI

33 

Qattan AT, Mulvey C, Crawford M, Natale DA and Godovac-Zimmermann J: Quantitative organelle proteomics of MCF-7 breast cancer cells reveals multiple subcellular locations for proteins in cellular functional processes. J Proteome Res. 9:495–508. 2010. View Article : Google Scholar

34 

Hassani M, Hellebrekers P, Chen N, van Aalst C, Bongers S, Hietbrink F, Koenderman L and Vrisekoop N: On the origin of low-density neutrophils. J Leukoc Biol. 107:809–818. 2020. View Article : Google Scholar : PubMed/NCBI

35 

Shi W, Wang Y, Zhang C, Jin H, Zeng Z, Wei L, Tian Y, Zhang D and Sun G: Isolation and purification of immune cells from the liver. Int Immunopharmacol. 85:1066322020. View Article : Google Scholar : PubMed/NCBI

36 

Grist TM, Canon CL, Fishman EK, Kohi MP and Mossa-Basha M: Short-, mid-, and long-term strategies to manage the shortage of iohexol. Radiology. 304:289–293. 2022. View Article : Google Scholar : PubMed/NCBI

37 

Liang S, Su M, Liu B, Liu R, Zheng H, Qiu W and Zhang Z: Evaluation of blood induced influence for high-definition intravascular ultrasound (HD-IVUS). IEEE Trans Ultrason Ferroelectr Freq Control. 69:98–105. 2022. View Article : Google Scholar

38 

Warwick J and Holness J: Measurement of glomerular filtration rate. Semin Nucl Med. 52:453–466. 2022. View Article : Google Scholar : PubMed/NCBI

39 

Elgamal S, Cocucci E, Sass EJ, Mo XM, Blissett AR, Calomeni EP, Rogers KA, Woyach JA, Bhat SA, Muthusamy N, et al: Optimizing extracellular vesicles' isolation from chronic lymphocytic leukemia patient plasma and cell line supernatant. JCI Insight. 6:e1379372021. View Article : Google Scholar

40 

Inoue T, Kusumoto S, Iio E, Ogawa S, Suzuki T, Yagi S, Kaneko A, Matsuura K, Aoyagi K and Tanaka Y: Clinical efficacy of a novel, high-sensitivity HBcrAg assay in the management of chronic hepatitis B and HBV reactivation. J Hepatol. 75:302–310. 2021. View Article : Google Scholar : PubMed/NCBI

41 

Tóth EÁ, Turiák L, Visnovitz T, Cserép C, Mázló A, Sódar BW, Försönits AI, Petővári G, Sebestyén A, Komlósi Z, et al: Formation of a protein corona on the surface of extracellular vesicles in blood plasma. J Extracell Vesicles. 10:e121402021. View Article : Google Scholar : PubMed/NCBI

42 

Veerman RE, Teeuwen L, Czarnewski P, Güclüler Akpinar G, Sandberg A, Cao X, Pernemalm M, Orre LM, Gabrielsson S and Eldh M: Molecular evaluation of five different isolation methods for extracellular vesicles reveals different clinical applicability and subcellular origin. J Extracell Vesicles. 10:e121282021. View Article : Google Scholar : PubMed/NCBI

43 

Cartuche L, Reyes-Batlle M, Sifaoui I, Arberas-Jiménez I, Piñero JE, Fernández JJ, Lorenzo-Morales J and Díaz-Marrero AR: Antiamoebic activities of indolocarbazole metabolites isolated from streptomyces sanyensis cultures. Mar Drugs. 17:5882019. View Article : Google Scholar :

44 

Jiang S, Zhang E, Ruan H, Ma J, Zhao X, Zhu Y, Xiu X, Han N, Li J, Zhang H, et al: Actinomycin V induces apoptosis associated with mitochondrial and PI3K/AKT pathways in human CRC cells. Mar Drugs. 19:5992021. View Article : Google Scholar : PubMed/NCBI

45 

Li K, Liang Z, Chen W, Luo X, Fang W, Liao S, Lin X, Yang B, Wang J, Tang L, et al: Iakyricidins A-D, antiproliferative piericidin analogues bearing a carbonyl group or cyclic skeleton from streptomyces iakyrus SCSIO NS104. J Org Chem. 84:12626–12631. 2019. View Article : Google Scholar : PubMed/NCBI

46 

Liu L, Zhu H, Wu W, Shen Y, Lin X, Wu Y, Liu L, Tang J, Zhou Y, Sun F and Lin HW: Neoantimycin F, a streptomyces-derived natural product induces mitochondria-related apoptotic death in human non-small cell lung cancer cells. Front Pharmacol. 10:10422019. View Article : Google Scholar :

47 

Rawat PS, Jaiswal A, Khurana A, Bhatti JS and Navik U: Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management. Biomed Pharmacother. 139:1117082021. View Article : Google Scholar : PubMed/NCBI

48 

Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K and Hauser CJ: Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 464:104–107. 2010. View Article : Google Scholar : PubMed/NCBI

49 

Deng X, Liu J, Liu L, Sun X, Huang J and Dong J: Drp1-mediated mitochondrial fission contributes to baicalein-induced apoptosis and autophagy in lung cancer via activation of AMPK signaling pathway. Int J Biol Sci. 16:1403–1416. 2020. View Article : Google Scholar : PubMed/NCBI

50 

Ma ZJ, Lu L, Yang JJ, Wang XX, Su G, Wang ZL, Chen GH, Sun HM, Wang MY and Yang Y: Lariciresinol induces apoptosis in HepG2 cells via mitochondrial-mediated apoptosis pathway. Eur J Pharmacol. 821:1–10. 2018. View Article : Google Scholar

51 

Ke H, Dass S, Morrisey JM, Mather MW and Vaidya AB: The mitochondrial ribosomal protein L13 is critical for the structural and functional integrity of the mitochondrion in plasmodium falciparum. J Biol Chem. 293:8128–8137. 2018. View Article : Google Scholar : PubMed/NCBI

52 

Galvan DL, Green NH and Danesh FR: The hallmarks of mitochondrial dysfunction in chronic kidney disease. Kidney Int. 92:1051–1057. 2017. View Article : Google Scholar : PubMed/NCBI

53 

Wiemerslage L and Lee D: Quantification of mitochondrial morphology in neurites of dopaminergic neurons using multiple parameters. J Neurosci Methods. 262:56–65. 2016. View Article : Google Scholar : PubMed/NCBI

54 

Labarta E, de Los Santos MJ, Escribá MJ, Pellicer A and Herraiz S: Mitochondria as a tool for oocyte rejuvenation. Fertil Steril. 111:219–226. 2019. View Article : Google Scholar : PubMed/NCBI

55 

Li WQ, Wang Z, Hao S, He H, Wan Y, Zhu C, Sun LP, Cheng G and Zheng SY: Mitochondria-targeting polydopamine nanoparticles to deliver doxorubicin for overcoming drug resistance. ACS Appl Mater Interfaces. 9:16793–16802. 2017. View Article : Google Scholar : PubMed/NCBI

56 

Lin Y, Liu J, Bai R, Shi J, Zhu X, Liu J, Guo J, Zhang W, Liu H and Liu Z: Mitochondria-inspired nanoparticles with microenvironment-adapting capacities for on-demand drug delivery after ischemic injury. ACS Nano. 14:11846–11859. 2020. View Article : Google Scholar : PubMed/NCBI

57 

Smith GM and Gallo G: The role of mitochondria in axon development and regeneration. Dev Neurobiol. 78:221–237. 2018. View Article : Google Scholar :

58 

Bastian C, Day J, Politano S, Quinn J, Brunet S and Baltan S: Preserving mitochondrial structure and motility promotes recovery of white matter after ischemia. Neuromolecular Med. 21:484–492. 2019. View Article : Google Scholar : PubMed/NCBI

59 

Bhargava P and Schnellmann RG: Mitochondrial energetics in the kidney. Nat Rev Nephrol. 13:629–646. 2017. View Article : Google Scholar : PubMed/NCBI

60 

Granata C, Jamnick NA and Bishop DJ: Training-induced changes in mitochondrial content and respiratory function in human skeletal muscle. Sports Med. 48:1809–1828. 2018. View Article : Google Scholar : PubMed/NCBI

61 

Hammond K, Ryadnov MG and Hoogenboom BW: Atomic force microscopy to elucidate how peptides disrupt membranes. Biochim Biophys Acta Biomembr. 1863:1834472021. View Article : Google Scholar

62 

Heath GR, Kots E, Robertson JL, Lansky S, Khelashvili G, Weinstein H and Scheuring S: Localization atomic force microscopy. Nature. 594:385–390. 2021. View Article : Google Scholar : PubMed/NCBI

63 

Müller DJ, Dumitru AC, Lo Giudice C, Gaub HE, Hinterdorfer P, Hummer G, De Yoreo JJ, Dufrêne YF and Alsteens D: Atomic force microscopy-based force spectroscopy and multiparametric imaging of biomolecular and cellular systems. Chem Rev. 121:11701–11725. 2021. View Article : Google Scholar

64 

Vogt N: Atomic force microscopy in super-resolution. Nat Methods. 18:8592021. View Article : Google Scholar : PubMed/NCBI

65 

Kolossov VL, Sivaguru M, Huff J, Luby K, Kanakaraju K and Gaskins HR: Airyscan super-resolution microscopy of mitochondrial morphology and dynamics in living tumor cells. Microsc Res Tech. 81:115–128. 2018. View Article : Google Scholar

66 

Rocha EM, De Miranda B and Sanders LH: Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson's disease. Neurobiol Dis. 109:249–257. 2018. View Article : Google Scholar

67 

Szymański J, Janikiewicz J, Michalska B, Patalas-Krawczyk P, Perrone M, Ziółkowski W, Duszyński J, Pinton P, Dobrzyń A and Więckowski MR: Interaction of mitochondria with the endoplasmic reticulum and plasma membrane in calcium homeostasis, lipid trafficking and mitochondrial structure. Int J Mol Sci. 18:15762017. View Article : Google Scholar

68 

Adam N, Beattie TL and Riabowol K: Fluorescence microscopy methods for examining telomeres during cell aging. Ageing Res Rev. 68:1013202021. View Article : Google Scholar : PubMed/NCBI

69 

Huang L, Chen H, Luo Y, Rivenson Y and Ozcan A: Recurrent neural network-based volumetric fluorescence microscopy. Light Sci Appl. 10:622021. View Article : Google Scholar : PubMed/NCBI

70 

Thiele JC, Helmerich DA, Oleksiievets N, Tsukanov R, Butkevich E, Sauer M, Nevskyi O and Enderlein J: Confocal fluorescence-lifetime single-molecule localization microscopy. ACS Nano. 14:14190–14200. 2020. View Article : Google Scholar : PubMed/NCBI

71 

Zhang Y, Zong H, Zong C, Tan Y, Zhang M, Zhan Y and Cheng JX: Fluorescence-detected mid-infrared photothermal microscopy. J Am Chem Soc. 143:11490–11499. 2021. View Article : Google Scholar : PubMed/NCBI

72 

Alexander JF, Seua AV, Arroyo LD, Ray PR, Wangzhou A, Heiβ-Lückemann L, Schedlowski M, Price TJ, Kavelaars A and Heijnen CJ: Nasal administration of mitochondria reverses chemotherapy-induced cognitive deficits. Theranostics. 11:3109–3130. 2021. View Article : Google Scholar : PubMed/NCBI

73 

Dumitru AC, Stommen A, Koehler M, Cloos AS, Yang J, Leclercqz A, Tyteca D and Alsteens D: Probing PIEZO1 localization upon activation using high-resolution atomic force and confocal microscopy. Nano Lett. 21:4950–4958. 2021. View Article : Google Scholar : PubMed/NCBI

74 

Wu Y, Han X, Su Y, Glidewell M, Daniels JS, Liu J, Sengupta T, Rey-Suarez I, Fischer R, Patel A, et al: Multiview confocal super-resolution microscopy. Nature. 600:279–284. 2021. View Article : Google Scholar : PubMed/NCBI

75 

Yordanov S, Neuhaus K, Hartmann R, Díaz-Pascual F, Vidakovic L, Singh PK and Drescher K: Single-objective high-resolution confocal light sheet fluorescence microscopy for standard biological sample geometries. Biomed Opt Express. 12:3372–3391. 2021. View Article : Google Scholar : PubMed/NCBI

76 

Zhao Y, Raghuram A, Kim HK, Hielscher AH, Robinson JT and Veeraraghavan A: High resolution, deep imaging using confocal time-of-flight diffuse optical tomography. IEEE Trans Pattern Anal Mach Intell. 43:2206–2219. 2021. View Article : Google Scholar : PubMed/NCBI

77 

Dalecká M, Sabó J, Backová L, Rösel D, Brábek J, Benda A and Tolde O: Invadopodia structure in 3D environment resolved by near-infrared branding protocol combining correlative confocal and FIB-SEM microscopy. Int J Mol Sci. 22:78052021. View Article : Google Scholar : PubMed/NCBI

78 

Guo R, Barnea I and Shaked NT: Limited-angle tomographic phase microscopy utilizing confocal scanning fluorescence microscopy. Biomed Opt Express. 12:1869–1881. 2021. View Article : Google Scholar : PubMed/NCBI

79 

Lamers MM, van der Vaart J, Knoops K, Riesebosch S, Breugem TI, Mykytyn AZ, Beumer J, Schipper D, Bezstarosti K, Koopman CD, et al: An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells. EMBO J. 40:e1059122021. View Article : Google Scholar

80 

Messal HA, Almagro J, Zaw Thin M, Tedeschi A, Ciccarelli A, Blackie L, Anderson KI, Miguel-Aliaga I, van Rheenen J and Behrens A: Antigen retrieval and clearing for whole-organ immunofluorescence by FLASH. Nat Protoc. 16:239–262. 2021. View Article : Google Scholar

81 

Miyashita L, Foley G, Gill I, Gillmore G, Grigg J and Wertheim D: Confocal microscopy 3D imaging of diesel particulate matter. Environ Sci Pollut Res Int. 28:30384–30389. 2021. View Article : Google Scholar : PubMed/NCBI

82 

Restall BS, Kedarisetti P, Haven NJM, Martell MT and Zemp RJ: Multimodal 3D photoacoustic remote sensing and confocal fluorescence microscopy imaging. J Biomed Opt. 26:0965012021. View Article : Google Scholar :

83 

Rodriguez-Gallardo S, Kurokawa K, Sabido-Bozo S, Cortes-Gomez A, Perez-Linero AM, Aguilera-Romero A, Lopez S, Waga M, Nakano A and Muñiz M: Assay for dual cargo sorting into endoplasmic reticulum exit sites imaged by 3D super-resolution confocal live imaging microscopy (SCLIM). PLoS One. 16:e02581112021. View Article : Google Scholar : PubMed/NCBI

84 

Durand MJ, Ait-Aissa K, Levchenko V, Staruschenko A, Gutterman DD and Beyer AM: Visualization and quantification of mitochondrial structure in the endothelium of intact arteries. Cardiovasc Res. 115:1546–1556. 2019. View Article : Google Scholar :

85 

Bartolák-Suki E and Suki B: Tuning mitochondrial structure and function to criticality by fluctuation-driven mechanotransduction. Sci Rep. 10:4072020. View Article : Google Scholar : PubMed/NCBI

86 

Chandhok G, Lazarou M and Neumann B: Structure, function, and regulation of mitofusin-2 in health and disease. Biol Rev Camb Philos Soc. 93:933–949. 2018. View Article : Google Scholar

87 

Kowaltowski AJ, Menezes-Filho SL, Assali EA, Gonçalves IG, Cabral-Costa JV, Abreu P, Miller N, Nolasco P, Laurindo FRM, Bruni-Cardoso A and Shirihai OS: Mitochondrial morphology regulates organellar Ca2+ uptake and changes cellular Ca2+ homeostasis. FASEB J. 33:13176–13188. 2019. View Article : Google Scholar : PubMed/NCBI

88 

Csordás G, Weaver D and Hajnóczky G: Endoplasmic reticulum-mitochondrial contactology: Structure and signaling functions. Trends Cell Biol. 28:523–540. 2018. View Article : Google Scholar : PubMed/NCBI

89 

Xie LL, Shi F, Tan Z, Li Y, Bode AM and Cao Y: Mitochondrial network structure homeostasis and cell death. Cancer Sci. 109:3686–3694. 2018. View Article : Google Scholar : PubMed/NCBI

90 

Correia-Álvarez E, Keating JE, Glish G, Tarran R and Sassano MF: Reactive oxygen species, mitochondrial membrane potential, and cellular membrane potential are predictors of E-liquid induced cellular toxicity. Nicotine Tob Res. 22(Suppl 1): S4–S13. 2020. View Article : Google Scholar : PubMed/NCBI

91 

Zhou Y, Long Q, Wu H, Li W, Qi J, Wu Y, Xiang G, Tang H, Yang L, Chen K, et al: Topology-dependent, bifurcated mitochondrial quality control under starvation. Autophagy. 16:562–574. 2020. View Article : Google Scholar :

92 

Du R, Bei H, Jia L, Huang C, Chen Q, Wang J, Wu F, Chen J and Bo H: A low-cost, accurate method for detecting reticulocytes at different maturation stages based on changes in the mitochondrial membrane potential. J Pharmacol Toxicol Methods. 101:1066642020. View Article : Google Scholar

93 

Ganta KK, Mandal A and Chaubey B: Depolarization of mitochondrial membrane potential is the initial event in non-nucleoside reverse transcriptase inhibitor efavirenz induced cytotoxicity. Cell Biol Toxicol. 33:69–82. 2017. View Article : Google Scholar

94 

Dreier DA, Denslow ND and Martyniuk CJ: Computational in vitro toxicology uncovers chemical structures impairing mitochondrial membrane potential. J Chem Inf Model. 59:702–712. 2019. View Article : Google Scholar : PubMed/NCBI

95 

Lee JY, Lim W, Ham J, Kim J, You S and Song G: Ivermectin induces apoptosis of porcine trophectoderm and uterine luminal epithelial cells through loss of mitochondrial membrane potential, mitochondrial calcium ion overload, and reactive oxygen species generation. Pestic Biochem Physiol. 159:144–153. 2019. View Article : Google Scholar : PubMed/NCBI

96 

Tao L, Liu X, Da W, Tao Z and Zhu Y: Pycnogenol achieves neuroprotective effects in rats with spinal cord injury by stabilizing the mitochondrial membrane potential. Neurol Res. 42:597–604. 2020. View Article : Google Scholar : PubMed/NCBI

97 

Haider SZ, Mohanraj N, Markandeya YS, Joshi PG and Mehta B: Picture perfect: Imaging mitochondrial membrane potential changes in retina slices with minimal stray fluorescence. Exp Eye Res. 202:1083182021. View Article : Google Scholar

98 

Zhang G, Yang W, Zou P, Jiang F, Zeng Y, Chen Q, Sun L, Yang H, Zhou N, Wang X, et al: Mitochondrial functionality modifies human sperm acrosin activity, acrosome reaction capability and chromatin integrity. Hum Reprod. 34:3–11. 2019. View Article : Google Scholar

99 

Sakthivel R, Malar DS and Devi KP: Phytol shows anti-angiogenic activity and induces apoptosis in A549 cells by depolarizing the mitochondrial membrane potential. Biomed Pharmacother. 105:742–752. 2018. View Article : Google Scholar : PubMed/NCBI

100 

Alyasin A, Momeni HR and Mahdieh M: Aquaporin3 expression and the potential role of aquaporins in motility and mitochondrial membrane potential in human spermatozoa. Andrologia. 52:e135882020. View Article : Google Scholar : PubMed/NCBI

101 

Alpert NM, Guehl N, Ptaszek L, Pelletier-Galarneau M, Ruskin J, Mansour MC, Wooten D, Ma C, Takahashi K, Zhou Y, et al: Quantitative in vivo mapping of myocardial mitochondrial membrane potential. PLoS One. 13:e01909682018. View Article : Google Scholar : PubMed/NCBI

102 

Kuwahara Y, Roudkenar MH, Suzuki M, Urushihara Y and Fukumoto M, Saito Y and Fukumoto M: The Involvement of mitochondrial membrane potential in cross-resistance between radiation and docetaxel. Int J Radiat Oncol Biol Phys. 96:556–565. 2016. View Article : Google Scholar : PubMed/NCBI

103 

Marcondes NA, Terra SR, Lasta CS, Hlavac NRC, Dalmolin ML, Lacerda LA, Faulhaber GAM and González FHD: Comparison of JC-1 and MitoTracker probes for mitochondrial viability assessment in stored canine platelet concentrates: A flow cytometry study. Cytometry A. 95:214–218. 2019. View Article : Google Scholar

104 

Poznanski RR, Cacha LA, Ali J, Rizvi ZH, Yupapin P, Salleh SH and Bandyopadhyay A: Induced mitochondrial membrane potential for modeling solitonic conduction of electrotonic signals. PLoS One. 12:e01836772017. View Article : Google Scholar : PubMed/NCBI

105 

Georgakopoulos ND, Wells G and Campanella M: The pharmacological regulation of cellular mitophagy. Nat Chem Biol. 13:136–146. 2017. View Article : Google Scholar : PubMed/NCBI

106 

Bikas A, Jensen K, Patel A, Costello J, Kaltsas G, Hoperia V, Wartofsky L, Burman K and Vasko V: Mitotane induces mitochondrial membrane depolarization and apoptosis in thyroid cancer cells. Int J Oncol. 55:7–20. 2019.PubMed/NCBI

107 

Gloria A, Wegher L, Carluccio A, Valorz C, Robbe D and Contri A: Factors affecting staining to discriminate between bull sperm with greater and lesser mitochondrial membrane potential. Anim Reprod Sci. 189:51–59. 2018. View Article : Google Scholar

108 

Saraf KK, Kumaresan A, Chhillar S, Nayak S, Lathika S, Datta TK, Gahlot SC, Karan P, Verma K and Mohanty TK: Spermatozoa with high mitochondrial membrane potential and low tyrosine phosphorylation preferentially bind to oviduct explants in the water buffalo (Bubalus bubalis). Anim Reprod Sci. 180:30–36. 2017. View Article : Google Scholar : PubMed/NCBI

109 

Cano M, Datta S, Wang L, Liu T, Flores-Bellver M, Sachdeva M, Sinha D and Handa JT: Nrf2 deficiency decreases NADPH from impaired IDH shuttle and pentose phosphate pathway in retinal pigmented epithelial cells to magnify oxidative stress-induced mitochondrial dysfunction. Aging Cell. 20:e134442021. View Article : Google Scholar : PubMed/NCBI

110 

El Manaa W, Duplan E, Goiran T, Lauritzen I, Vaillant Beuchot L, Lacas-Gervais S, Morais VA, You H, Qi L and Salazar M: et al Transcription- and phosphorylation-dependent control of a functional interplay between XBP1s and PINK1 governs mitophagy and potentially impacts Parkinson disease pathophysiology. Autophagy. 17:4363–4385. 2021. View Article : Google Scholar : PubMed/NCBI

111 

Franco-Iborra S, Plaza-Zabala A, Montpeyo M, Sebastian D, Vila M and Martinez-Vicente M: Mutant HTT (huntingtin) impairs mitophagy in a cellular model of Huntington disease. Autophagy. 17:672–689. 2021. View Article : Google Scholar :

112 

Hamilton K, Krause K, Badr A, Daily K, Estfanous S, Eltobgy M, Khweek AA, Anne MNK, Carafice C, Baetzhold D, et al: Defective immunometabolism pathways in cystic fibrosis macrophages. J Cyst Fibros. 20:664–672. 2021. View Article : Google Scholar :

113 

Rabinovich-Nikitin I, Rasouli M, Reitz CJ, Posen I, Margulets V, Dhingra R, Khatua TN, Thliveris JA, Martino TA and Kirshenbaum LA: Mitochondrial autophagy and cell survival is regulated by the circadian clock gene in cardiac myocytes during ischemic stress. Autophagy. 17:3794–3812. 2021. View Article : Google Scholar : PubMed/NCBI

114 

Rovini A, Heslop K, Hunt EG, Morris ME, Fang D, Gooz M, Gerencser AA and Maldonado EN: Quantitative analysis of mitochondrial membrane potential heterogeneity in unsynchronized and synchronized cancer cells. FASEB J. 35:e211482021. View Article : Google Scholar

115 

Samuvel DJ, Li L, Krishnasamy Y, Gooz M, Takemoto K, Woster PM, Lemasters JJ and Zhong Z: Mitochondrial depolarization after acute ethanol treatment drives mitophagy in living mice. Autophagy. 1–15. 2022.Epub ahead of print. View Article : Google Scholar : PubMed/NCBI

116 

Wang Q and Hutt KJ: Evaluation of mitochondria in mouse oocytes following cisplatin exposure. J Ovarian Res. 14:652021. View Article : Google Scholar : PubMed/NCBI

117 

Yazdankhah M, Ghosh S, Shang P, Stepicheva N, Hose S, Liu H, Chamling X, Tian S, Sullivan MLG, Calderon MJ, et al: BNIP3L-mediated mitophagy is required for mitochondrial remodeling during the differentiation of optic nerve oligodendrocytes. Autophagy. 17:3140–3159. 2021. View Article : Google Scholar : PubMed/NCBI

118 

Young VC and Artigas P: Displacement of the Na+/K+ pump's transmembrane domains demonstrates conserved conformational changes in P-type 2 ATPases. Proc Natl Acad Sci USA. 118:e20193171182021. View Article : Google Scholar

119 

Cui Y, Duan W, Jin Y, Wo F, Xi F and Wu J: Graphene quantum dot-decorated luminescent porous silicon dressing for theranostics of diabetic wounds. Acta Biomater. 131:544–554. 2021. View Article : Google Scholar : PubMed/NCBI

120 

Kambe Y and Yamaoka T: Initial immune response to a FRET-based MMP sensor-immobilized silk fibroin hydrogel in vivo. Acta Biomater. 130:199–210. 2021. View Article : Google Scholar : PubMed/NCBI

121 

Feng R, Guo L, Fang J, Jia Y, Wang X, Wei Q and Yu X: Construction of the FRET pairs for the visualization of mitochondria membrane potential in dual emission colors. Anal Chem. 91:3704–3709. 2019. View Article : Google Scholar : PubMed/NCBI

122 

Lee H, Kim SJ, Shin H and Kim YP: Collagen-immobilized extracellular FRET reporter for visualizing protease activity secreted by living cells. ACS Sens. 5:655–664. 2020. View Article : Google Scholar : PubMed/NCBI

123 

Liu L, Chu H, Yang J, Sun Y, Ma P and Song D: Construction of a magnetic-fluorescent-plasmonic nanosensor for the determination of MMP-2 activity based on SERS-fluorescence dual-mode signals. Biosens Bioelectron. 212:1143892022. View Article : Google Scholar : PubMed/NCBI

124 

Zhan Y, Ling S, Huang H, Zhang Y, Chen G, Huang S, Li C, Guo W and Wang Q: Rapid unperturbed-tissue analysis for intraoperative cancer diagnosis using an enzyme-activated NIR-II nanoprobe. Angew Chem Int Ed Engl. 60:2637–2642. 2021. View Article : Google Scholar

125 

Wang C, Wang G, Li X, Wang K, Fan J, Jiang K, Guo Y and Zhang H: Highly sensitive fluorescence molecular switch for the ratio monitoring of trace change of mitochondrial membrane potential. Anal Chem. 89:11514–11519. 2017. View Article : Google Scholar : PubMed/NCBI

126 

Rao M, Jaber BL and Balakrishnan VS: Chronic kidney disease and acquired mitochondrial myopathy. Curr Opin Nephrol Hypertens. 27:113–120. 2018. View Article : Google Scholar

127 

Zhu SC, Chen C, Wu YN, Ahmed M, Kitmitto A, Greenstein AS, Kim SJ, Shao YF and Zhang YH: Cardiac complex II activity is enhanced by fat and mediates greater mitochondrial oxygen consumption following hypoxic re-oxygenation. Pflugers Arch. 472:367–374. 2020. View Article : Google Scholar : PubMed/NCBI

128 

Kurhaluk N, Lukash O, Nosar V, Portnychenko A, Portnichenko V, Wszedybyl-Winklewska M and Winklewski PJ: Liver mitochondrial respiratory plasticity and oxygen uptake evoked by cobalt chloride in rats with low and high resistance to extreme hypobaric hypoxia. Can J Physiol Pharmacol. 97:392–399. 2019. View Article : Google Scholar : PubMed/NCBI

129 

Acetoze G, Champagne J, Ramsey JJ and Rossow HA: Liver mitochondrial oxygen consumption and efficiency of milk production in lactating Holstein cows supplemented with copper, manganese and zinc. J Anim Physiol Anim Nutr (Berl). 102:e787–e797. 2018. View Article : Google Scholar

130 

Kalyanaraman B, Cheng G, Hardy M, Ouari O, Lopez M, Joseph J, Zielonka J and Dwinell MB: A review of the basics of mitochondrial bioenergetics, metabolism, and related signaling pathways in cancer cells: Therapeutic targeting of tumor mitochondria with lipophilic cationic compounds. Redox Biol. 14:316–327. 2018. View Article : Google Scholar

131 

Banh RS, Iorio C, Marcotte R, Xu Y, Cojocari D, Rahman AA, Pawling J, Zhang W, Sinha A, Rose CM, et al: PTP1B controls non-mitochondrial oxygen consumption by regulating RNF213 to promote tumour survival during hypoxia. Nat Cell Biol. 18:803–813. 2016. View Article : Google Scholar : PubMed/NCBI

132 

Campos JC, Queliconi BB, Bozi LHM, Bechara LRG, Dourado PMM, Andres AM, Jannig PR, Gomes KMS, Zambelli VO, Rocha-Resende C, et al: Exercise reestablishes autophagic flux and mitochondrial quality control in heart failure. Autophagy. 13:1304–1317. 2017. View Article : Google Scholar : PubMed/NCBI

133 

Rossow HA, Acetoze G, Champagne J and Ramsey JJ: Measuring liver mitochondrial oxygen consumption and proton leak kinetics to estimate mitochondrial respiration in holstein dairy cattle. J Vis Exp. 2018. View Article : Google Scholar : PubMed/NCBI

134 

Morimoto N, Hashimoto S, Yamanaka M, Nakano T, Satoh M, Nakaoka Y, Iwata H, Fukui A, Morimoto Y and Shibahara H: Mitochondrial oxygen consumption rate of human embryos declines with maternal age. J Assist Reprod Genet. 37:1815–1821. 2020. View Article : Google Scholar : PubMed/NCBI

135 

Darr CR, Cortopassi GA, Datta S, Varner DD and Meyers SA: Mitochondrial oxygen consumption is a unique indicator of stallion spermatozoal health and varies with cryopreservation media. Theriogenology. 86:1382–1392. 2016. View Article : Google Scholar : PubMed/NCBI

136 

Müller ME, Vikstrom S, König M, Schlichting R, Zarfl C, Zwiener C and Escher BI: Mitochondrial toxicity of selected micropollutants, their mixtures, and surface water samples measured by the oxygen consumption rate in cells. Environ Toxicol Chem. 38:1000–1011. 2019. View Article : Google Scholar : PubMed/NCBI

137 

Thomas LW and Ashcroft M: Exploring the molecular interface between hypoxia-inducible factor signalling and mitochondria. Cell Mol Life Sci. 76:1759–1777. 2019. View Article : Google Scholar : PubMed/NCBI

138 

Espinosa JA, Pohan G, Arkin MR and Markossian S: Real-time assessment of mitochondrial toxicity in HepG2 cells using the Seahorse extracellular flux analyzer. Curr Protoc. 1:e752021. View Article : Google Scholar : PubMed/NCBI

139 

Fu Y, Wang D, Wang H, Cai M, Li C, Zhang X, Chen H, Hu Y, Zhang X, Ying M, et al: TSPO deficiency induces mitochondrial dysfunction, leading to hypoxia, angiogenesis, and a growth-promoting metabolic shift toward glycolysis in glioblastoma. Neuro Oncol. 22:240–252. 2020.

140 

Gu X, Ma Y, Liu Y and Wan Q: Measurement of mitochondrial respiration in adherent cells by Seahorse XF96 cell mito stress Test. STAR Protoc. 2:1002452021. View Article : Google Scholar : PubMed/NCBI

141 

Eagleson KL, Villaneuva M, Southern RM and Levitt P: Proteomic and mitochondrial adaptations to early-life stress are distinct in juveniles and adults. Neurobiol Stress. 13:1002512020. View Article : Google Scholar : PubMed/NCBI

142 

Maremanda KP, Sundar IK and Rahman I: Role of inner mitochondrial protein OPA1 in mitochondrial dysfunction by tobacco smoking and in the pathogenesis of COPD. Redox Biol. 45:1020552021. View Article : Google Scholar : PubMed/NCBI

143 

Nishida M, Yamashita N, Ogawa T, Koseki K, Warabi E, Ohue T, Komatsu M, Matsushita H, Kakimi K, Kawakami E, et al: Mitochondrial reactive oxygen species trigger metformin-dependent antitumor immunity via activation of Nrf2/mTORC1/p62 axis in tumor-infiltrating CD8T lymphocytes. J Immunother Cancer. 9:e0029542021. View Article : Google Scholar : PubMed/NCBI

144 

Nishida Y, Nawaz A, Kado T, Takikawa A, Igarashi Y, Onogi Y, Wada T, Sasaoka T, Yamamoto S, Sasahara M, et al: Astaxanthin stimulates mitochondrial biogenesis in insulin resistant muscle via activation of AMPK pathway. J Cachexia Sarcopenia Muscle. 11:241–258. 2020. View Article : Google Scholar : PubMed/NCBI

145 

Sabogal-Guáqueta AM, Hobbie F, Keerthi A, Oun A, Kortholt A, Boddeke E and Dolga A: Linalool attenuates oxidative stress and mitochondrial dysfunction mediated by glutamate and NMDA toxicity. Biomed Pharmacother. 118:1092952019. View Article : Google Scholar : PubMed/NCBI

146 

Tian T, Zhang Y, Wu T, Yang L, Chen C, Li N, Li Y, Xu S, Fu Z, Cui X, et al: miRNA profiling in the hippocampus of attention-deficit/hyperactivity disorder rats. J Cell Biochem. 120:3621–3629. 2019. View Article : Google Scholar

147 

Ooi K, Hu L, Feng Y, Han C, Ren X, Qian X, Huang H, Chen S, Shi Q, Lin H, et al: Sigma-1 receptor activation suppresses microglia M1 polarization via regulating endoplasmic reticulum-mitochondria contact and mitochondrial functions in stress-induced hypertension rats. Mol Neurobiol. 58:6625–6646. 2021. View Article : Google Scholar : PubMed/NCBI

148 

Shetty T, Park B and Corson TW: Measurement of mitochondrial respiration in the murine retina using a Seahorse extracellular flux analyzer. STAR Protoc. 2:1005332021. View Article : Google Scholar : PubMed/NCBI

149 

Wang SH, Zhu XL, Wang F, Chen SX, Chen ZT, Qiu Q, Liu WH, Wu MX, Deng BQ, Xie Y, et al: LncRNA H19 governs mitophagy and restores mitochondrial respiration in the heart through Pink1/Parkin signaling during obesity. Cell Death Dis. 12:5572021. View Article : Google Scholar : PubMed/NCBI

150 

Andersen JV, Jakobsen E, Waagepetersen HS and Aldana BI: Distinct differences in rates of oxygen consumption and ATP synthesis of regionally isolated non-synaptic mouse brain mitochondria. J Neurosci Res. 97:961–974. 2019. View Article : Google Scholar : PubMed/NCBI

151 

Hubbard WB, Joseph B, Spry M, Vekaria HJ, Saatman KE and Sullivan PG: Acute mitochondrial impairment underlies prolonged cellular dysfunction after repeated mild traumatic brain injuries. J Neurotrauma. 36:1252–1263. 2019. View Article : Google Scholar

152 

McAlpin BR, Mahalingam R, Singh AK, Dharmaraj S, Chrisikos TT, Boukelmoune N, Kavelaars A and Heijnen CJ: HDAC6 inhibition reverses long-term doxorubicin-induced cognitive dysfunction by restoring microglia homeostasis and synaptic integrity. Theranostics. 12:603–619. 2022. View Article : Google Scholar : PubMed/NCBI

153 

Raut S, Patel R and Al-Ahmad AJ: Presence of a mutation in PSEN1 or PSEN2 gene is associated with an impaired brain endothelial cell phenotype in vitro. Fluids Barriers CNS. 18:32021. View Article : Google Scholar : PubMed/NCBI

154 

Algieri C, Trombetti F, Pagliarani A, Ventrella V and Nesci S: The mitochondrial F1FO -ATPase exploits the dithiol redox state to modulate the permeability transition pore. Arch Biochem Biophys. 712:1090272021. View Article : Google Scholar

155 

Sun C, Liu X, Wang B, Wang Z, Liu Y, Di C, Si J, Li H, Wu Q, Xu D, et al: Endocytosis-mediated mitochondrial transplantation: Transferring normal human astrocytic mitochondria into glioma cells rescues aerobic respiration and enhances radiosensitivity. Theranostics. 9:3595–3607. 2019. View Article : Google Scholar : PubMed/NCBI

156 

Sun JY, Zhao SJ, Wang HB, Hou YJ, Mi QJ, Yang MF, Yuan H, Ni QB, Sun BL and Zhang ZY: Ifenprodil improves long-term neurologic deficits through antagonizing glutamate-induced excitotoxicity after experimental subarachnoid hemorrhage. Transl Stroke Res. 12:1067–1080. 2021. View Article : Google Scholar : PubMed/NCBI

157 

Boyman L, Karbowski M and Lederer WJ: Regulation of mitochondrial ATP production: Ca2+ signaling and quality control. Trends Mol Med. 26:21–39. 2020. View Article : Google Scholar

158 

Bravo-Sagua R, Parra V, López-Crisosto C, Díaz P, Quest AF and Lavandero S: Calcium transport and signaling in mitochondria. Compr Physiol. 7:623–634. 2017. View Article : Google Scholar : PubMed/NCBI

159 

Marchi S, Patergnani S, Missiroli S, Morciano G, Rimessi A, Wieckowski MR, Giorgi C and Pinton P: Mitochondrial and endoplasmic reticulum calcium homeostasis and cell death. Cell Calcium. 69:62–72. 2018. View Article : Google Scholar

160 

Chow J, Rahman J, Achermann JC, Dattani MT and Rahman S: Mitochondrial disease and endocrine dysfunction. Nat Rev Endocrinol. 13:92–104. 2017. View Article : Google Scholar

161 

Cieluch A, Uruska A and Zozulinska-Ziolkiewicz D: Can we prevent mitochondrial dysfunction and diabetic cardiomyopathy in type 1 diabetes mellitus? Pathophysiology and treatment options. Int J Mol Sci. 21:28522020. View Article : Google Scholar :

162 

Ding XW, Robinson M, Li R, Aldhowayan H, Geetha T and Babu JR: Mitochondrial dysfunction and beneficial effects of mitochondria-targeted small peptide SS-31 in diabetes mellitus and Alzheimer's disease. Pharmacol Res. 171:1057832021. View Article : Google Scholar : PubMed/NCBI

163 

Fisher JJ, Vanderpeet CL, Bartho LA, McKeating DR, Cuffe JSM, Holland OJ and Perkins AV: Mitochondrial dysfunction in placental trophoblast cells experiencing gestational diabetes mellitus. J Physiol. 599:1291–1305. 2021. View Article : Google Scholar

164 

Jelenik T and Roden M: Mitochondrial plasticity in obesity and diabetes mellitus. Antioxid Redox Signal. 19:258–268. 2013. View Article : Google Scholar :

165 

Rovira-Llopis S, Bañuls C, Diaz-Morales N, Hernandez-Mijares A, Rocha M and Victor VM: Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications. Redox Biol. 11:637–645. 2017. View Article : Google Scholar : PubMed/NCBI

166 

Zhao H, Li T, Wang K, Zhao F, Chen J, Xu G, Zhao J, Li T, Chen L, Li L, et al: AMPK-mediated activation of MCU stimulates mitochondrial Ca2+ entry to promote mitotic progression. Nat Cell Biol. 21:476–486. 2019. View Article : Google Scholar : PubMed/NCBI

167 

Calvo-Rodriguez M, Hou SS, Snyder AC, Kharitonova EK, Russ AN, Das S, Fan Z, Muzikansky A, Garcia-Alloza M, Serrano-Pozo A, et al: Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer's disease. Nat Commun. 11:21462020. View Article : Google Scholar : PubMed/NCBI

168 

Bhatti JS, Bhatti GK and Reddy PH: Mitochondrial dysfunction and oxidative stress in metabolic disorders-a step towards mitochondria based therapeutic strategies. Biochim Biophys Acta Mol Basis Dis. 1863:1066–1077. 2017. View Article : Google Scholar

169 

Guo Q, Bi J, Wang H and Zhang X: Mycobacterium tuberculosis ESX-1-secreted substrate protein EspC promotes mycobacterial survival through endoplasmic reticulum stress-mediated apoptosis. Emerg Microbes Infect. 10:19–36. 2021. View Article : Google Scholar :

170 

Galla L, Vajente N, Pendin D, Pizzo P, Pozzan T and Greotti E: Generation and characterization of a new FRET-Based Ca2+ sensor targeted to the nucleus. Int J Mol Sci. 22:99452021. View Article : Google Scholar

171 

Isshiki M, Nishimoto M, Mizuno R and Fujita T: FRET-based sensor analysis reveals caveolae are spatially distinct Ca2+ stores in endothelial cells. Cell Calcium. 54:395–403. 2013. View Article : Google Scholar : PubMed/NCBI

172 

Laskaratou D, Fernández GS, Coucke Q, Fron E, Rocha S, Hofkens J, Hendrix J and Mizuno H: Quantification of FRET-induced angular displacement by monitoring sensitized acceptor anisotropy using a dim fluorescent donor. Nat Commun. 12:25412021. View Article : Google Scholar : PubMed/NCBI

173 

Nagai T, Ibata K, Park ES, Kubota M, Mikoshiba K and Miyawaki A: A variant of yellow fluorescent protein with fast and efficient maturation for cell-biological applications. Nat Biotechnol. 20:87–90. 2002. View Article : Google Scholar

174 

Ucar H, Watanabe S, Noguchi J, Morimoto Y, Iino Y, Yagishita S, Takahashi N and Kasai H: Mechanical actions of dendritic-spine enlargement on presynaptic exocytosis. Nature. 600:686–689. 2021. View Article : Google Scholar : PubMed/NCBI

175 

Yoon S, Pan Y, Shung K and Wang Y: FRET-based Ca2+ biosensor single cell imaging interrogated by high-frequency ultrasound. Sensors (Basel). 20. pp. 49982020, View Article : Google Scholar

176 

Chen J, Qiu M, Zhang S, Li B, Li D, Huang X, Qian Z, Zhao J, Wang Z and Tang D: A calcium phosphate drug carrier loading with 5-fluorouracil achieving a synergistic effect for pancreatic cancer therapy. J Colloid Interface Sci. 605:263–273. 2022. View Article : Google Scholar

177 

Fan Y and Simmen T: Mechanistic connections between endoplasmic reticulum (ER) Redox Control And Mitochondrial Metabolism. Cells. 8:10712019. View Article : Google Scholar :

178 

Shoshan-Barmatz V, Nahon-Crystal E, Shteinfer-Kuzmine A and Gupta R: VDAC1, mitochondrial dysfunction, and Alzheimer's disease. Pharmacol Res. 131:87–101. 2018. View Article : Google Scholar : PubMed/NCBI

179 

Country MW and Jonz MG: Mitochondrial KATP channels stabilize intracellular Ca2+ during hypoxia in retinal horizontal cells of goldfish (Carassius auratus). J Exp Biol. 224:jeb2426342021. View Article : Google Scholar : PubMed/NCBI

180 

Davidson SM, Padró T, Bollini S, Vilahur G, Duncker DJ, Evans PC, Guzik T, Hoefer IE, Waltenberger J, Wojta J and Weber C: Progress in cardiac research: From rebooting cardiac regeneration to a complete cell atlas of the heart. Cardiovasc Res. 117:2161–2174. 2021. View Article : Google Scholar : PubMed/NCBI

181 

Leduc-Gaudet JP, Hussain SNA, Barreiro E and Gouspillou G: Mitochondrial dynamics and mitophagy in skeletal muscle health and aging. Int J Mol Sci. 22:81792021. View Article : Google Scholar : PubMed/NCBI

182 

Li S, Chen J, Liu M, Chen Y, Wu Y, Li Q, Ma T, Gao J, Xia Y, Fan M, et al: Protective effect of HINT2 on mitochondrial function via repressing MCU complex activation attenuates cardiac microvascular ischemia-reperfusion injury. Basic Res Cardiol. 116:652021. View Article : Google Scholar : PubMed/NCBI

183 

Mollazadeh H, Tavana E, Fanni G, Bo S, Banach M, Pirro M, von Haehling S, Jamialahmadi T and Sahebkar A: Effects of statins on mitochondrial pathways. J Cachexia Sarcopenia Muscle. 12:237–251. 2021. View Article : Google Scholar : PubMed/NCBI

184 

Nakamura T, Ogawa M, Kojima K, Takayanagi S, Ishihara S, Hattori K, Naguro I and Ichijo H: The mitochondrial Ca2+ uptake regulator, MICU1, is involved in cold stress-induced ferroptosis. EMBO Rep. 22:e515322021. View Article : Google Scholar

185 

Chen M, Mu L, Wang S, Cao X, Liang S, Wang Y, She G, Yang J, Wang Y and Shi W: A single silicon nanowire-based ratiometric biosensor for Ca2+ at various locations in a neuron. ACS Chem Neurosci. 11:1283–1290. 2020. View Article : Google Scholar : PubMed/NCBI

186 

Jiang Y, Fang Y, Ye Y, Xu X, Wang B, Gu J, Aschner M, Chen J and Lu R: Anti-cancer effects of 3,3'-diindolylmethane on human hepatocellular carcinoma cells is enhanced by calcium ionophore: The role of cytosolic Ca2+ and p38 MAPK. Front Pharmacol. 10:11672019. View Article : Google Scholar

187 

Mata-Martínez E, Sánchez-Tusie AA, Darszon A, Mayorga LS, Treviño CL and De Blas GA: Epac activation induces an extracellular Ca2+-independent Ca2+ wave that triggers acrosome reaction in human spermatozoa. Andrology. 9:1227–1241. 2021. View Article : Google Scholar

188 

Wacquier B, Combettes L and Dupont G: Dual dynamics of mitochondrial permeability transition pore opening. Sci Rep. 10:39242020. View Article : Google Scholar : PubMed/NCBI

189 

Nesci S, Trombetti F, Ventrella V and Pagliarani A: From the Ca2+-activated F1FO-ATPase to the mitochondrial permeability transition pore: An overview. Biochimie. 152:85–93. 2018. View Article : Google Scholar : PubMed/NCBI

190 

Cui Y, Pan M, Ma J, Song X, Cao W and Zhang P: Recent progress in the use of mitochondrial membrane permeability transition pore in mitochondrial dysfunction-related disease therapies. Mol Cell Biochem. 476:493–506. 2021. View Article : Google Scholar

191 

Chinopoulos C: Mitochondrial permeability transition pore: Back to the drawing board. Neurochem Int. 117:49–54. 2018. View Article : Google Scholar

192 

Briston T, Selwood DL, Szabadkai G and Duchen MR: Mitochondrial permeability transition: A molecular lesion with multiple drug targets. Trends Pharmacol Sci. 40:50–70. 2019. View Article : Google Scholar

193 

Rottenberg H and Hoek JB: The path from mitochondrial ROS to aging runs through the mitochondrial permeability transition pore. Aging Cell. 16:943–955. 2017. View Article : Google Scholar : PubMed/NCBI

194 

Zhou B, Kreuzer J, Kumsta C, Wu L, Kamer KJ, Cedillo L, Zhang Y, Li S, Kacergis MC, Webster CM, et al: Mitochondrial permeability uncouples elevated autophagy and lifespan extension. Cell. 177:299–314.e16. 2019. View Article : Google Scholar : PubMed/NCBI

195 

Baines CP and Gutiérrez-Aguilar M: The still uncertain identity of the channel-forming unit(s) of the mitochondrial permeability transition pore. Cell Calcium. 73:121–130. 2018. View Article : Google Scholar : PubMed/NCBI

196 

Ying Z, Xiang G, Zheng L, Tang H, Duan L, Lin X, Zhao Q, Chen K, Wu Y, Xing G, et al: Short-term mitochondrial permeability transition pore opening modulates histone lysine methylation at the early phase of somatic cell reprogramming. Cell Metab. 28:935–945.e5. 2018. View Article : Google Scholar : PubMed/NCBI

197 

Burke PJ: Mitochondria, bioenergetics and apoptosis in cancer. Trends Cancer. 3:857–870. 2017. View Article : Google Scholar : PubMed/NCBI

198 

Pérez MJ, Ponce DP, Aranguiz A, Behrens MI and Quintanilla RA: Mitochondrial permeability transition pore contributes to mitochondrial dysfunction in fibroblasts of patients with sporadic Alzheimer's disease. Redox Biol. 19:290–300. 2018. View Article : Google Scholar : PubMed/NCBI

199 

Kalani K, Yan SF and Yan SS: Mitochondrial permeability transition pore: A potential drug target for neurodegeneration. Drug Discov Today. 23:1983–1989. 2018. View Article : Google Scholar : PubMed/NCBI

200 

Naryzhnaya NV, Maslov LN and Oeltgen PR: Pharmacology of mitochondrial permeability transition pore inhibitors. Drug Dev Res. 80:1013–1030. 2019. View Article : Google Scholar : PubMed/NCBI

201 

Shah SS, Lannon H, Dias L, Zhang JY, Alper SL, Pollak MR and Friedman DJ: APOL1 kidney risk variants induce cell death via mitochondrial translocation and opening of the mitochondrial permeability transition pore. J Am Soc Nephrol. 30:2355–2368. 2019. View Article : Google Scholar : PubMed/NCBI

202 

Gao G, Wang Z, Lu L, Duan C, Wang X and Yang H: Morphological analysis of mitochondria for evaluating the toxicity of α-synuclein in transgenic mice and isolated preparations by atomic force microscopy. Biomed Pharmacother. 96:1380–1388. 2017. View Article : Google Scholar : PubMed/NCBI

203 

Ghosh P, Bhoumik A, Saha S, Mukherjee S, Azmi S, Ghosh JK and Dungdung SR: Spermicidal efficacy of VRP, a synthetic cationic antimicrobial peptide, inducing apoptosis and membrane disruption. J Cell Physiol. 233:1041–1050. 2018. View Article : Google Scholar

204 

Jiang S, Zu Y, Wang Z, Zhang Y and Fu Y: Involvement of mitochondrial permeability transition pore opening in 7-xylosyl-10-deacetylpaclitaxel-induced apoptosis. Planta Med. 77:1005–1012. 2011. View Article : Google Scholar : PubMed/NCBI

205 

Tricaud N, Gautier B, Berthelot J, Gonzalez S and Van Hameren G: Traumatic and diabetic schwann cell demyelination is triggered by a transient mitochondrial calcium release through voltage dependent anion channel 1. Biomedicines. 10:14472022. View Article : Google Scholar : PubMed/NCBI

206 

Mukherjee R, Mareninova OA, Odinokova IV, Huang W, Murphy J, Chvanov M, Javed MA, Wen L, Booth DM, Cane MC, et al: Mechanism of mitochondrial permeability transition pore induction and damage in the pancreas: Inhibition prevents acute pancreatitis by protecting production of ATP. Gut. 65:1333–1346. 2016. View Article : Google Scholar

207 

Urbani A, Giorgio V, Carrer A, Franchin C, Arrigoni G, Jiko C, Abe K, Maeda S, Shinzawa-Itoh K, Bogers JFM, et al: Purified F-ATP synthase forms a Ca2+-dependent high-conductance channel matching the mitochondrial permeability transition pore. Nat Commun. 10:43412019. View Article : Google Scholar

208 

Aqawi M, Sionov RV, Gallily R, Friedman M and Steinberg D: Anti-bacterial properties of cannabigerol toward streptococcus mutans. Front Microbiol. 12:6564712021. View Article : Google Scholar :

209 

Asperti M, Bellini S, Grillo E, Gryzik M, Cantamessa L, Ronca R, Maccarinelli F, Salvi A, De Petro G, Arosio P, et al: H-ferritin suppression and pronounced mitochondrial respiration make hepatocellular carcinoma cells sensitive to RSL3-induced ferroptosis. Free Radic Biol Med. 169:294–303. 2021. View Article : Google Scholar : PubMed/NCBI

210 

Daniyal M, Liu Y, Yang Y, Xiao F, Fan J, Yu H, Qiu Y, Liu B, Wang W and Yuhui Q: Anti-gastric cancer activity and mechanism of natural compound 'Heilaohulignan C' isolated from Kadsura coccinea. Phytother Res. 35:3977–3987. 2021. View Article : Google Scholar : PubMed/NCBI

211 

Datki Z, Acs E, Balazs E, Sovany T, Csoka I, Zsuga K, Kalman J and Galik-Olah Z: Exogenic production of bioactive filamentous biopolymer by monogonant rotifers. Ecotoxicol Environ Saf. 208:1116662021. View Article : Google Scholar : PubMed/NCBI

212 

Ge Y, Wang C, Zhang W, Lai S, Wang D and Wang L: Coassembly behavior and rheological properties of a β-hairpin peptide with dicarboxylates. Langmuir. 37:11657–11664. 2021. View Article : Google Scholar : PubMed/NCBI

213 

He A, Wang L, Wang Q, Luan W and Qi F: Protective effects of micronized fat against ultraviolet B-induced photoaging. Plast Reconstr Surg. 145:712–720. 2020. View Article : Google Scholar : PubMed/NCBI

214 

Jiang Q, Su DY, Wang ZZ, Liu C, Sun YN, Cheng H, Li XM and Yan B: Retina as a window to cerebral dysfunction following studies with circRNA signature during neurodegeneration. Theranostics. 11:1814–1827. 2021. View Article : Google Scholar : PubMed/NCBI

215 

Kirk NM, Vieson MD, Selting KA and Reinhart JM: Cytotoxicity of cultured canine primary hepatocytes exposed to itraconazole is decreased by pre-treatment with glutathione. Front Vet Sci. 8:6217322021. View Article : Google Scholar : PubMed/NCBI

216 

Lan HY, An P, Liu QP, Chen YY, Yu YY, Luan X, Tang JY and Zhang H: Aidi injection induces apoptosis of hepatocellular carcinoma cells through the mitochondrial pathway. J Ethnopharmacol. 274:1140732021. View Article : Google Scholar : PubMed/NCBI

217 

Li C, Sun G, Chen B, Xu L, Ye Y, He J, Bao Z, Zhao P, Miao Z, Zhao L, et al: Nuclear receptor coactivator 4-mediated ferritinophagy contributes to cerebral ischemia-induced ferroptosis in ischemic stroke. Pharmacol Res. 174:1059332021. View Article : Google Scholar : PubMed/NCBI

218 

Liu X, Xing S, Xu Y, Chen R, Lin C and Guo L: 3-Amino-1,2,4-triazole-derived graphitic carbon nitride for photodynamic therapy. Spectrochim Acta A Mol Biomol Spectrosc. 250:1193632021. View Article : Google Scholar : PubMed/NCBI

219 

Suo L, Liu C, Zhang QY, Yao MD, Ma Y, Yao J, Jiang Q and Yan B: METTL3-mediated N 6-methyladenosine modification governs pericyte dysfunction during diabetes-induced retinal vascular complication. Theranostics. 12:277–289. 2022. View Article : Google Scholar :

220 

Panel M, Ruiz I, Brillet R, Lafdil F, Teixeira-Clerc F, Nguyen CT, Calderaro J, Gelin M, Allemand F, Guichou JF, et al: Small-molecule inhibitors of cyclophilins block opening of the mitochondrial permeability transition pore and protect mice from hepatic ischemia/reperfusion injury. Gastroenterology. 157:1368–1382. 2019. View Article : Google Scholar : PubMed/NCBI

221 

Winquist RJ and Gribkoff VK: Targeting putative components of the mitochondrial permeability transition pore for novel therapeutics. Biochem Pharmacol. 177:1139952020. View Article : Google Scholar : PubMed/NCBI

222 

Yu CH, Davidson S, Harapas CR, Hilton JB, Mlodzianoski MJ, Laohamonthonkul P, Louis C, Low RRJ, Moecking J, De Nardo D, et al: TDP-43 triggers mitochondrial DNA release via mPTP to activate cGAS/STING in ALS. Cell. 183:636–649.e18. 2020. View Article : Google Scholar : PubMed/NCBI

223 

Wu S and Zou MH: AMPK, mitochondrial function, and cardiovascular disease. Int J Mol Sci. 21:49872020. View Article : Google Scholar :

224 

Lee P, Chandel NS and Simon MC: Cellular adaptation to hypoxia through hypoxia inducible factors and beyond. Nat Rev Mol Cell Biol. 21:268–283. 2020. View Article : Google Scholar : PubMed/NCBI

225 

Tan KY, Li CY, Li YF, Fei J, Yang B, Fu YJ and Li F: Real-time monitoring ATP in mitochondrion of living cells: A specific fluorescent probe for ATP by dual recognition sites. Anal Chem. 89:1749–1756. 2017. View Article : Google Scholar : PubMed/NCBI

226 

Arai S, Kriszt R, Harada K, Looi LS, Matsuda S, Wongso D, Suo S, Ishiura S, Tseng YH, Raghunath M, et al: RGB-color intensiometric indicators to visualize spatiotemporal dynamics of ATP in single cells. Angew Chem Int Ed Engl. 57:10873–10878. 2018. View Article : Google Scholar : PubMed/NCBI

227 

Potter M, Newport E and Morten KJ: The Warburg effect: 80 Years on. Biochem Soc Trans. 44:1499–1505. 2016. View Article : Google Scholar : PubMed/NCBI

228 

Nesci S, Pagliarani A, Algieri C and Trombetti F: Mitochondrial F-type ATP synthase: multiple enzyme functions revealed by the membrane-embedded FO structure. Crit Rev Biochem Mol Biol. 55:309–321. 2020. View Article : Google Scholar : PubMed/NCBI

229 

Schönfeld P and Wojtczak L: Short- and medium-chain fatty acids in energy metabolism: The cellular perspective. J Lipid Res. 57:943–954. 2016. View Article : Google Scholar : PubMed/NCBI

230 

Chistiakov DA, Shkurat TP, Melnichenko AA, Grechko AV and Orekhov AN: The role of mitochondrial dysfunction in cardiovascular disease: A brief review. Ann Med. 50:121–127. 2018. View Article : Google Scholar

231 

Costa R, Peruzzo R, Bachmann M, Montà GD, Vicario M, Santinon G, Mattarei A, Moro E, Quintana-Cabrera R, Scorrano L, et al: Impaired mitochondrial ATP production downregulates Wnt signaling via ER stress induction. Cell Rep. 28:1949–1960.e6. 2019. View Article : Google Scholar : PubMed/NCBI

232 

Rambold AS and Pearce EL: Mitochondrial dynamics at the interface of immune cell metabolism and function. Trends Immunol. 39:6–18. 2018. View Article : Google Scholar

233 

Roger AJ, Muñoz-Gómez SA and Kamikawa R: The origin and diversification of mitochondria. Curr Biol. 27:R1177–R1192. 2017. View Article : Google Scholar : PubMed/NCBI

234 

Guntur AR, Gerencser AA, Le PT, DeMambro VE, Bornstein SA, Mookerjee SA, Maridas DE, Clemmons DE, Brand MD and Rosen CJ: Osteoblast-like MC3T3-E1 cells prefer glycolysis for ATP production but adipocyte-like 3T3-L1 cells prefer oxidative phosphorylation. J Bone Miner Res. 33:1052–1065. 2018. View Article : Google Scholar : PubMed/NCBI

235 

Depaoli MR, Karsten F, Madreiter-Sokolowski CT, Klec C, Gottschalk B, Bischof H, Eroglu E, Waldeck-Weiermair M, Simmen T, Graier WF and Malli R: Real-time imaging of mitochondrial ATP dynamics reveals the metabolic setting of single cells. Cell Rep. 25:501–512.e3. 2018. View Article : Google Scholar : PubMed/NCBI

236 

Hampl V, Čepička I and Eliáš M: Was the mitochondrion necessary to start eukaryogenesis? Trends Microbiol. 27:96–104. 2019. View Article : Google Scholar

237 

Beamer E, Conte G and Engel T: ATP release during seizures-a critical evaluation of the evidence. Brain Res Bull. 151:65–73. 2019. View Article : Google Scholar : PubMed/NCBI

238 

Buckel W, Hetzel M and Kim J: ATP-driven electron transfer in enzymatic radical reactions. Curr Opin Chem Biol. 8:462–467. 2004. View Article : Google Scholar : PubMed/NCBI

239 

Chen H and Zhang YPJ: Enzymatic regeneration and conservation of ATP: Challenges and opportunities. Crit Rev Biotechnol. 41:16–33. 2021. View Article : Google Scholar

240 

Dorr BM and Fuerst DE: Enzymatic amidation for industrial applications. Curr Opin Chem Biol. 43:127–133. 2018. View Article : Google Scholar : PubMed/NCBI

241 

Finley D and Prado MA: The proteasome and its network: Engineering for adaptability. Cold Spring Harb Perspect Biol. 12:a0339852020. View Article : Google Scholar

242 

Hammler D, Marx A and Zumbusch A: Fluorescencelifetime-sensitive probes for monitoring ATP cleavage. Chemistry. 24:15329–15335. 2018. View Article : Google Scholar : PubMed/NCBI

243 

Ishida A, Yamada Y and Kamidate T: Colorimetric method for enzymatic screening assay of ATP using Fe(III)-xylenol orange complex formation. Anal Bioanal Chem. 392:987–994. 2008. View Article : Google Scholar : PubMed/NCBI

244 

Midelfort CF and Rose IA: A stereochemical method for detection of ATP terminal phosphate transfer in enzymatic reactions. Glutamine synthetase J Biol Chem. 251:5881–5887. 1976. View Article : Google Scholar

245 

Ušaj M, Moretto L, Vemula V, Salhotra A and Månsson A: Single molecule turnover of fluorescent ATP by myosin and actomyosin unveil elusive enzymatic mechanisms. Commun Biol. 4:642021. View Article : Google Scholar : PubMed/NCBI

246 

Vasta JD, Corona CR, Wilkinson J, Zimprich CA, Hartnett JR, Ingold MR, Zimmerman K, Machleidt T, Kirkland TA, Huwiler KG, et al: Quantitative, wide-spectrum kinase profiling in live cells for assessing the effect of cellular ATP on target engagement. Cell Chem Biol. 25:206–214.e11. 2018. View Article : Google Scholar :

247 

Klier PEZ, Martin JG and Miller EW: Imaging reversible mitochondrial membrane potential dynamics with a masked rhodamine voltage reporter. J Am Chem Soc. 143:4095–4099. 2021. View Article : Google Scholar : PubMed/NCBI

248 

Mita M, Sugawara I, Harada K, Ito M, Takizawa M, Ishida K, Ueda H, Kitaguchi T and Tsuboi T: Development of red genetically encoded biosensor for visualization of intracellular glucose dynamics. Cell Chem Biol. 29:98–108.e4. 2022. View Article : Google Scholar

249 

Murata O, Shindo Y, Ikeda Y, Iwasawa N, Citterio D, Oka K and Hiruta Y: Near-infrared fluorescent probes for imaging of intracellular Mg2+ and application to multi-color imaging of Mg2+, ATP, and mitochondrial membrane potential. Anal Chem. 92:966–974. 2020. View Article : Google Scholar

250 

Billingham LK, Stoolman JS, Vasan K, Rodriguez AE, Poor TA, Szibor M, Jacobs HT, Reczek CR, Rashidi A, Zhang P, et al: Mitochondrial electron transport chain is necessary for NLRP3 inflammasome activation. Nat Immunol. 23:692–704. 2022. View Article : Google Scholar : PubMed/NCBI

251 

Fernström J, Mellon SH, McGill MA, Picard M, Reus VI, Hough CM, Lin J, Epel ES, Wolkowitz OM and Lindqvist D: Blood-based mitochondrial respiratory chain function in major depression. Transl Psychiatry. 11:5932021. View Article : Google Scholar : PubMed/NCBI

252 

Spinelli JB, Rosen PC, Sprenger HG, Puszynska AM, Mann JL, Roessler JM, Cangelosi AL, Henne A, Condon KJ, Zhang T, et al: Fumarate is a terminal electron acceptor in the mammalian electron transport chain. Science. 374:1227–1237. 2021. View Article : Google Scholar : PubMed/NCBI

253 

Vercellino I and Sazanov LA: The assembly, regulation and function of the mitochondrial respiratory chain. Nat Rev Mol Cell Biol. 23:141–161. 2022. View Article : Google Scholar

254 

Colaço HG, Barros A, Neves-Costa A, Seixas E, Pedroso D, Velho T, Willmann KL, Faisca P, Grabmann G, Yi HS, et al: Tetracycline antibiotics induce host-dependent disease tolerance to infection. Immunity. 54:53–67.e7. 2021. View Article : Google Scholar :

255 

Dennerlein S, Wang C and Rehling P: Plasticity of mitochondrial translation. Trends Cell Biol. 27:712–721. 2017. View Article : Google Scholar : PubMed/NCBI

256 

Diebold LP, Gil HJ, Gao P, Martinez CA, Weinberg SE and Chandel NS: Mitochondrial complex III is necessary for endothelial cell proliferation during angiogenesis. Nat Metab. 1:158–171. 2019. View Article : Google Scholar : PubMed/NCBI

257 

Flønes IH, Ricken G, Klotz S, Lang A, Ströbel T, Dölle C, Kovacs GG and Tzoulis C: Mitochondrial respiratory chain deficiency correlates with the severity of neuropathology in sporadic Creutzfeldt-Jakob disease. Acta Neuropathol Commun. 8:502020. View Article : Google Scholar : PubMed/NCBI

258 

Manczak M, Kandimalla R, Yin X and Reddy PH: Mitochondrial division inhibitor 1 reduces dynamin-related protein 1 and mitochondrial fission activity. Hum Mol Genet. 28:177–199. 2019. View Article : Google Scholar :

259 

Markevich NI, Galimova MH and Markevich LN: Hysteresis and bistability in the succinate-CoQ reductase activity and reactive oxygen species production in the mitochondrial respiratory complex II. Redox Biol. 37:1016302020. View Article : Google Scholar : PubMed/NCBI

260 

Mazat JP, Devin A and Ransac S: Modelling mitochondrial ROS production by the respiratory chain. Cell Mol Life Sci. 77:455–465. 2020. View Article : Google Scholar

261 

Timón-Gómez A, Garlich J, Stuart RA, Ugalde C and Barrientos A: Distinct roles of mitochondrial HIGD1A and HIGD2A in respiratory complex and supercomplex biogenesis. Cell Rep. 31:1076072020. View Article : Google Scholar : PubMed/NCBI

262 

Grünewald A, Kumar KR and Sue CM: New insights into the complex role of mitochondria in Parkinson's disease. Prog Neurobiol. 177:73–93. 2019. View Article : Google Scholar

263 

Ansó E, Weinberg SE, Diebold LP, Thompson BJ, Malinge S, Schumacker PT, Liu X, Zhang Y, Shao Z, Steadman M, et al: The mitochondrial respiratory chain is essential for haematopoietic stem cell function. Nat Cell Biol. 19:614–625. 2017. View Article : Google Scholar : PubMed/NCBI

264 

Wang HW, Zhu SQ, Liu J, Miao CY, Zhang Y and Zhou BH: Fluoride-induced renal dysfunction via respiratory chain complex abnormal expression and fusion elevation in mice. Chemosphere. 238:1246072020. View Article : Google Scholar

265 

Weiland D, Brachvogel B, Hornig-Do HT, Neuhaus JFG, Holzer T, Tobin DJ, Niessen CM, Wiesner RJ and Baris OR: Imbalance of mitochondrial respiratory chain complexes in the epidermis induces severe skin inflammation. J Invest Dermatol. 138:132–140. 2018. View Article : Google Scholar

266 

Weinberg SE, Singer BD, Steinert EM, Martinez CA, Mehta MM, Martínez-Reyes I, Gao P, Helmin KA, Abdala-Valencia H, Sena LA, et al: Mitochondrial complex III is essential for suppressive function of regulatory T cells. Nature. 565:495–499. 2019. View Article : Google Scholar : PubMed/NCBI

267 

Wu M, Gu J, Zong S, Guo R, Liu T and Yang M: Research journey of respirasome. Protein Cell. 11:318–338. 2020. View Article : Google Scholar : PubMed/NCBI

268 

Yamada S, Ozaki H and Noguchi K: The mitochondrial respiratory chain maintains the photosynthetic electron flow in Arabidopsis thaliana leaves under high-light stress. Plant Cell Physiol. 61:283–295. 2020. View Article : Google Scholar

269 

Yamashita K, Miyazaki T, Fukuda Y, Mitsuyama J, Saijo T, Shimamura S, Yamamoto K, Imamura Y, Izumikawa K, Yanagihara K, et al: The novel arylamidine T-2307 selectively disrupts yeast mitochondrial function by inhibiting respiratory chain complexes. Antimicrob Agents Chemother. 63:e00374–19. 2019. View Article : Google Scholar : PubMed/NCBI

270 

Fernandez-Vizarra E and Zeviani M: Mitochondrial disorders of the OXPHOS system. FEBS Lett. 595:1062–1106. 2021. View Article : Google Scholar

271 

Hernansanz-Agustín P, Choya-Foces C, Carregal-Romero S, Ramos E, Oliva T, Villa-Piña T, Moreno L, Izquierdo-Álvarez A, Cabrera-García JD, Cortés A, et al: Na+ controls hypoxic signalling by the mitochondrial respiratory chain. Nature. 586:287–291. 2020. View Article : Google Scholar

272 

Kobayashi A, Azuma K, Ikeda K and Inoue S: Mechanisms underlying the regulation of mitochondrial respiratory chain complexes by nuclear steroid receptors. Int J Mol Sci. 21:66832020. View Article : Google Scholar :

273 

Martínez-Reyes I, Cardona LR, Kong H, Vasan K, McElroy GS, Werner M, Kihshen H, Reczek CR, Weinberg SE, Gao P, et al: Mitochondrial ubiquinol oxidation is necessary for tumour growth. Nature. 585:288–292. 2020. View Article : Google Scholar : PubMed/NCBI

274 

Castellana S, Biagini T, Petrizzelli F, Parca L, Panzironi N, Caputo V, Vescovi AL, Carella M and Mazza T: MitImpact 3: Modeling the residue interaction network of the respiratory chain subunits. Nucleic Acids Res. 49(D1): D1282–D1288. 2021. View Article : Google Scholar :

275 

Wang M, Ren X, Wang L, Lu X, Han L, Zhang X and Feng J: A functional analysis of mitochondrial respiratory chain cytochrome bc1 complex in gaeumannomyces tritici by RNA silencing as a possible target of carabrone. Mol Plant Pathol. 21:1529–1544. 2020. View Article : Google Scholar : PubMed/NCBI

276 

Mirali S, Botham A, Voisin V, Xu C, St-Germain J, Sharon D, Hoff FW, Qiu Y, Hurren R, Gronda M, et al: The mitochondrial peptidase, neurolysin, regulates respiratory chain supercomplex formation and is necessary for AML viability. Sci Transl Med. 12:eaaz82642020. View Article : Google Scholar : PubMed/NCBI

277 

Heyman E, Daussin F, Wieczorek V, Caiazzo R, Matran R, Berthon P, Aucouturier J, Berthoin S, Descatoire A, Leclair E, et al: Muscle oxygen supply and use in type 1 diabetes, from ambient air to the mitochondrial respiratory chain: Is there a limiting step? Diabetes Care. 43:209–218. 2020. View Article : Google Scholar

278 

Lobo-Jarne T, Pérez-Pérez R, Fontanesi F, Timón-Gómez A, Wittig I, Peñas A, Serrano-Lorenzo P, García-Consuegra I, Arenas J, Martín MA, et al: Multiple pathways coordinate assembly of human mitochondrial complex IV and stabilization of respiratory supercomplexes. EMBO J. 39:e1039122020. View Article : Google Scholar : PubMed/NCBI

279 

Mohanraj K, Wasilewski M, Benincá C, Cysewski D, Poznanski J, Sakowska P, Bugajska Z, Deckers M, Dennerlein S, Fernandez-Vizarra E, et al: Inhibition of proteasome rescues a pathogenic variant of respiratory chain assembly factor COA7. EMBO Mol Med. 11:e95612019. View Article : Google Scholar : PubMed/NCBI

280 

Formosa LE, Dibley MG, Stroud DA and Ryan MT: Building a complex complex: Assembly of mitochondrial respiratory chain complex I. Semin Cell Dev Biol. 76:154–162. 2018. View Article : Google Scholar

281 

Gao M, Yi J, Zhu J, Minikes AM, Monian P, Thompson CB and Jiang X: Role of mitochondria in ferroptosis. Mol Cell. 73:354–363.e3. 2019. View Article : Google Scholar :

282 

Maclean AE, Hertle AP, Ligas J, Bock R, Balk J and Meyer EH: Absence of complex I is associated with diminished respiratory chain function in european mistletoe. Curr Biol. 28:1614–1619.e3. 2018. View Article : Google Scholar : PubMed/NCBI

283 

Senkler J, Rugen N, Eubel H, Hegermann J and Braun HP: Absence of complex I implicates rearrangement of the respiratory chain in European mistletoe. Curr Biol. 28:1606–1613.e4. 2018. View Article : Google Scholar : PubMed/NCBI

284 

Signes A and Fernandez-Vizarra E: Assembly of mammalian oxidative phosphorylation complexes I-V and supercomplexes. Essays Biochem. 62:255–270. 2018. View Article : Google Scholar : PubMed/NCBI

285 

Kazak L, Chouchani ET, Stavrovskaya IG, Lu GZ, Jedrychowski MP, Egan DF, Kumari M, Kong X, Erickson BK, Szpyt J, et al: UCP1 deficiency causes brown fat respiratory chain depletion and sensitizes mitochondria to calcium overload-induced dysfunction. Proc Natl Acad Sci USA. 114:7981–7986. 2017. View Article : Google Scholar : PubMed/NCBI

286 

Kozlov AV, Lancaster JR Jr, Meszaros AT and Weidinger A: Mitochondria-meditated pathways of organ failure upon inflammation. Redox Biol. 13:170–181. 2017. View Article : Google Scholar : PubMed/NCBI

287 

Letts JA and Sazanov LA: Clarifying the supercomplex: The higher-order organization of the mitochondrial electron transport chain. Nat Struct Mol Biol. 24:800–808. 2017. View Article : Google Scholar : PubMed/NCBI

288 

Guo R, Zong S, Wu M, Gu J and Yang M: Architecture of Human Mitochondrial Respiratory Megacomplex I2III2IV2. Cell. 170:1247–1257.e12. 2017. View Article : Google Scholar

289 

Jian C, Xu F, Hou T, Sun T, Li J, Cheng H and Wang X: Deficiency of PHB complex impairs respiratory supercomplex formation and activates mitochondrial flashes. J Cell Sci. 130:2620–2630. 2017.PubMed/NCBI

290 

Ndi M, Marin-Buera L, Salvatori R, Singh AP and Ott M: Biogenesis of the bc1 complex of the mitochondrial respiratory chain. J Mol Biol. 430:3892–3905. 2018. View Article : Google Scholar : PubMed/NCBI

291 

Priesnitz C and Becker T: Pathways to balance mitochondrial translation and protein import. Genes Dev. 32:1285–1296. 2018. View Article : Google Scholar : PubMed/NCBI

292 

Lin KH, Xie A, Rutter JC, Ahn YR, Lloyd-Cowden JM, Nichols AG, Soderquist RS, Koves TR, Muoio DM, MacIver NJ, et al: Systematic dissection of the metabolic-apoptotic interface in AML reveals heme biosynthesis to be a regulator of drug sensitivity. Cell Metab. 29:1217–1231.e7. 2019. View Article : Google Scholar : PubMed/NCBI

293 

Lobo-Jarne T and Ugalde C: Respiratory chain supercomplexes: Structures, function and biogenesis. Semin Cell Dev Biol. 76:179–190. 2018. View Article : Google Scholar :

294 

Tsai YL, Coady TH, Lu L, Zheng D, Alland I, Tian B, Shneider NA and Manley JL: ALS/FTD-associated protein FUS induces mitochondrial dysfunction by preferentially sequestering respiratory chain complex mRNAs. Genes Dev. 34:785–805. 2020. View Article : Google Scholar : PubMed/NCBI

295 

Balsa E, Soustek MS, Thomas A, Cogliati S, García-Poyatos C, Martín-García E, Jedrychowski M, Gygi SP, Enriquez JA and Puigserver P: ER and nutrient stress promote assembly of respiratory chain supercomplexes through the PERK-eIF2α axis. Mol Cell. 74:877–890e6. 2019. View Article : Google Scholar

296 

Chinopoulos C: Acute sources of mitochondrial NAD+ during respiratory chain dysfunction. Exp Neurol. 327:1132182020. View Article : Google Scholar

297 

Cogliati S, Lorenzi I, Rigoni G, Caicci F and Soriano ME: Regulation of mitochondrial electron transport chain assembly. J Mol Biol. 430:4849–4873. 2018. View Article : Google Scholar : PubMed/NCBI

298 

Nagao T, Shintani Y, Hayashi T, Kioka H, Kato H, Nishida Y, Yamazaki S, Tsukamoto O, Yashirogi S, Yazawa I, et al: Higd1a improves respiratory function in the models of mitochondrial disorder. FASEB J. 34:1859–1871. 2020. View Article : Google Scholar : PubMed/NCBI

299 

Vankayala R and Hwang KC: Near-infrared-light-activatable nanomaterial-mediated phototheranostic nanomedicines: An emerging paradigm for cancer treatment. Adv Mater. 30:e17063202018. View Article : Google Scholar : PubMed/NCBI

300 

Wang S, Zhang Z, Wei S, He F, Li Z, Wang HH, Huang Y and Nie Z: Near-infrared light-controllable MXene hydrogel for tunable on-demand release of therapeutic proteins. Acta Biomater. 130:138–148. 2021. View Article : Google Scholar : PubMed/NCBI

301 

Zhang S, Weinberg S, DeBerge M, Gainullina A, Schipma M, Kinchen JM, Ben-Sahra I, Gius DR, Yvan-Charvet L, Chandel NS, et al: Efferocytosis fuels requirements of fatty acid oxidation and the electron transport chain to polarize macrophages for tissue repair. Cell Metab. 29:443–456.e5. 2019. View Article : Google Scholar : PubMed/NCBI

302 

Luo X, Gong X, Su L, Lin H, Yang Z, Yan X and Gao J: Activatable mitochondria-targeting organoarsenic prodrugs for bioenergetic cancer therapy. Angew Chem Int Ed Engl. 60:1403–1410. 2021. View Article : Google Scholar

303 

Jiang H, Zhang XW, Liao QL, Wu WT, Liu YL and Huang WH: Electrochemical monitoring of paclitaxel-induced ROS release from mitochondria inside single cells. Small. 15:e19017872019. View Article : Google Scholar : PubMed/NCBI

304 

Kaplan P, Tatarkova Z, Sivonova MK, Racay P and Lehotsky J: Homocysteine and mitochondria in cardiovascular and cerebrovascular systems. Int J Mol Sci. 21:76982020. View Article : Google Scholar :

305 

Koch RE, Josefson CC and Hill GE: Mitochondrial function, ornamentation, and immunocompetence. Biol Rev Camb Philos Soc. 92:1459–1474. 2017. View Article : Google Scholar

306 

Zhang L, Wang X, Cueto R, Effi C, Zhang Y, Tan H, Qin X, Ji Y, Yang X and Wang H: Biochemical basis and metabolic interplay of redox regulation. Redox Biol. 26:1012842019. View Article : Google Scholar : PubMed/NCBI

307 

Zhu X, Liu G, Bu Y, Zhang J, Wang L, Tian Y, Yu J, Wu Z and Zhou H: In situ monitoring of mitochondria regulating cell viability by the RNA-specific fluorescent photosensitizer. Anal Chem. 92:10815–10821. 2020. View Article : Google Scholar : PubMed/NCBI

308 

Blanco FJ, Valdes AM and Rego-Pérez I: Mitochondrial DNA variation and the pathogenesis of osteoarthritis phenotypes. Nat Rev Rheumatol. 14:327–340. 2018. View Article : Google Scholar : PubMed/NCBI

309 

Fuhrmann DC and Brüne B: Mitochondrial composition and function under the control of hypoxia. Redox Biol. 12:208–215. 2017. View Article : Google Scholar : PubMed/NCBI

310 

Lee JH and Paull TT: Mitochondria at the crossroads of ATM-mediated stress signaling and regulation of reactive oxygen species. Redox Biol. 32:1015112020. View Article : Google Scholar : PubMed/NCBI

311 

Madreiter-Sokolowski CT, Thomas C and Ristow M: Interrelation between ROS and Ca2+ in aging and age-related diseases. Redox Biol. 36:1016782020. View Article : Google Scholar

312 

Angelova PR, Esteras N and Abramov AY: Mitochondria and lipid peroxidation in the mechanism of neurodegeneration: Finding ways for prevention. Med Res Rev. 41:770–784. 2021. View Article : Google Scholar

313 

van der Reest J, Nardini Cecchino G, Haigis MC and Kordowitzki P: Mitochondria: Their relevance during oocyte ageing. Ageing Res Rev. 70:1013782021. View Article : Google Scholar : PubMed/NCBI

314 

Martins WK, Santos NF, Rocha CS, Bacellar IOL, Tsubone TM, Viotto AC, Matsukuma AY, Abrantes ABP, Siani P, Dias LG and Baptista MS: Parallel damage in mitochondria and lysosomes is an efficient way to photoinduce cell death. Autophagy. 15:259–279. 2019. View Article : Google Scholar :

315 

Kleih M, Böpple K, Dong M, Gaißler A, Heine S, Olayioye MA, Aulitzky WE and Essmann F: Direct impact of cisplatin on mitochondria induces ROS production that dictates cell fate of ovarian cancer cells. Cell Death Dis. 10:8512019. View Article : Google Scholar : PubMed/NCBI

316 

Sidlauskaite E, Gibson JW, Megson IL, Whitfield PD, Tovmasyan A, Batinic-Haberle I, Murphy MP, Moult PR and Cobley JN: Mitochondrial ROS cause motor deficits induced by synaptic inactivity: Implications for synapse pruning. Redox Biol. 16:344–351. 2018. View Article : Google Scholar : PubMed/NCBI

317 

Yang J, Chen Z, Liu N and Chen Y: Ribosomal protein L10 in mitochondria serves as a regulator for ROS level in pancreatic cancer cells. Redox Biol. 19:158–165. 2018. View Article : Google Scholar : PubMed/NCBI

318 

Erard M, Dupré-Crochet S and Nüße O: Biosensors for spatiotemporal detection of reactive oxygen species in cells and tissues. Am J Physiol Regul Integr Comp Physiol. 314:R667–R683. 2018. View Article : Google Scholar : PubMed/NCBI

319 

Jiang X, Wang L, Carroll SL, Chen J, Wang MC and Wang J: Challenges and opportunities for small-molecule fluorescent probes in redox biology applications. Antioxid Redox Signal. 29:518–540. 2018. View Article : Google Scholar : PubMed/NCBI

320 

Ortega-Villasante C, Burén S, Barón-Sola Á, Martínez F and Hernández LE: In vivo ROS and redox potential fluorescent detection in plants: Present approaches and future perspectives. Methods. 109:92–104. 2016. View Article : Google Scholar : PubMed/NCBI

321 

Ortega-Villasante C, Burén S, Blázquez-Castro A, Barón-Sola Á and Hernández LE: Fluorescent in vivo imaging of reactive oxygen species and redox potential in plants. Free Radic Biol Med. 122:202–220. 2018. View Article : Google Scholar : PubMed/NCBI

322 

Dragišić Maksimović J, Mojović M, Vučinić Ž and Maksimović V: Spatial distribution of apoplastic antioxidative constituents in maize root. Physiol Plant. 173:818–828. 2021. View Article : Google Scholar

323 

Emoto MC, Sato-Akaba H, Hamaue N, Kawanishi K, Koshino H, Shimohama S and Fujii HG: Early detection of redox imbalance in the APPswe/PS1dE9 mouse model of Alzheimer's disease by in vivo electron paramagnetic resonance imaging. Free Radic Biol Med. 172:9–18. 2021. View Article : Google Scholar : PubMed/NCBI

324 

Gotham JP, Li R, Tipple TE, Lancaster JR Jr, Liu T and Li Q: Quantitation of spin probe-detectable oxidants in cells using electron paramagnetic resonance spectroscopy: To probe or to trap? Free Radic Biol Med. 154:84–94. 2020. View Article : Google Scholar : PubMed/NCBI

325 

He L, Li MX, Chen F, Yang SS, Ding J, Ding L and Ren NQ: Novel coagulation waste-based Fe-containing carbonaceous catalyst as peroxymonosulfate activator for pollutants degradation: Role of ROS and electron transfer pathway. J Hazard Mater. 417:1261132021. View Article : Google Scholar : PubMed/NCBI

326 

Hinoshita M, Abe T, Sato A, Maeda Y and Takeyoshi M: Development of a new photosafety test method based on singlet oxygen generation detected using electron spin resonance. J Appl Toxicol. 41:247–255. 2021. View Article : Google Scholar

327 

Matsumoto KI, Ueno M, Shoji Y and Nakanishi I: Heavy-ion beam-induced reactive oxygen species and redox reactions. Free Radic Res. 55:450–460. 2021. View Article : Google Scholar : PubMed/NCBI

328 

Mendoza C, Désert A, Khrouz L, Páez CA, Parola S and Heinrichs B: Heterogeneous singlet oxygen generation: In-operando visible light EPR spectroscopy. Environ Sci Pollut Res Int. 28:25124–25129. 2021. View Article : Google Scholar

329 

Okazaki Y, Ishidzu Y, Ito F, Tanaka H, Hori M and Toyokuni S: L-Dehydroascorbate efficiently degrades non-thermal plasma-induced hydrogen peroxide. Arch Biochem Biophys. 700:1087622021. View Article : Google Scholar : PubMed/NCBI

330 

Prasad A, Manoharan RR, Sedlářová M and Pospíšil P: Free radical-mediated protein radical formation in differentiating monocytes. Int J Mol Sci. 22:99632021. View Article : Google Scholar : PubMed/NCBI

331 

Yamaguchi M, Ma T, Tadaki D, Hirano-Iwata A, Watanabe Y, Kanetaka H, Fujimori H, Takemoto E and Niwano M: Bactericidal activity of bulk nanobubbles through active oxygen species generation. Langmuir. Aug 2–2021.Epub ahead of print. View Article : Google Scholar : PubMed/NCBI

332 

Zhang K, Deng R, Teng X, Li Y, Sun Y, Ren X and Li J: Direct visualization of single-nucleotide variation in mtDNA using a CRISPR/Cas9-mediated proximity ligation assay. J Am Chem Soc. 140:11293–11301. 2018. View Article : Google Scholar : PubMed/NCBI

333 

Moriyama M, Koshiba T and Ichinohe T: Influenza A virus M2 protein triggers mitochondrial DNA-mediated antiviral immune responses. Nat Commun. 10:46242019. View Article : Google Scholar : PubMed/NCBI

334 

Baumann K: mtDNA robs nuclear dNTPs. Nat Rev Mol Cell Biol. 20:6632019. View Article : Google Scholar : PubMed/NCBI

335 

Lazo S, Noren Hooten N, Green J, Eitan E, Mode NA, Liu QR, Zonderman AB, Ezike N, Mattson MP, Ghosh P and Evans MK: Mitochondrial DNA in extracellular vesicles declines with age. Aging Cell. 20:e132832021. View Article : Google Scholar :

336 

Li D, Du X, Guo X, Zhan L, Li X, Yin C, Chen C, Li M, Li B, Yang H and Xing J: Site-specific selection reveals selective constraints and functionality of tumor somatic mtDNA mutations. J Exp Clin Cancer Res. 36:1682017. View Article : Google Scholar : PubMed/NCBI

337 

Medeiros TC and Graef M: Autophagy determines mtDNA copy number dynamics during starvation. Autophagy. 15:178–179. 2019. View Article : Google Scholar

338 

Fontana GA and Gahlon HL: Mechanisms of replication and repair in mitochondrial DNA deletion formation. Nucleic Acids Res. 48:11244–11258. 2020. View Article : Google Scholar : PubMed/NCBI

339 

Wanrooij PH, Tran P, Thompson LJ, Carvalho G, Sharma S, Kreisel K, Navarrete C, Feldberg AL, Watt DL, Nilsson AK, et al: Elimination of rNMPs from mitochondrial DNA has no effect on its stability. Proc Natl Acad Sci USA. 117:14306–14313. 2020. View Article : Google Scholar : PubMed/NCBI

340 

Wei W and Chinnery PF: Inheritance of mitochondrial DNA in humans: Implications for rare and common diseases. J Intern Med. 287:634–644. 2020. View Article : Google Scholar : PubMed/NCBI

341 

Ignatenko O, Chilov D, Paetau I, de Miguel E, Jackson CB, Capin G, Paetau A, Terzioglu M, Euro L and Suomalainen A: Loss of mtDNA activates astrocytes and leads to spongiotic encephalopathy. Nat Commun. 9:702018. View Article : Google Scholar : PubMed/NCBI

342 

Kasahara T and Kato T: What can mitochondrial DNA analysis tell us about mood disorders? Biol Psychiatry. 83:731–738. 2018. View Article : Google Scholar

343 

Larsson NG and Wedell A: Mitochondria in human disease. J Intern Med. 287:589–591. 2020. View Article : Google Scholar : PubMed/NCBI

344 

Bagge EK, Fujimori-Tonou N, Kubota-Sakashita M, Kasahara T and Kato T: Unbiased PCR-free spatio-temporal mapping of the mtDNA mutation spectrum reveals brain region-specific responses to replication instability. BMC Biol. 18:1502020. View Article : Google Scholar : PubMed/NCBI

345 

Chiang JL, Shukla P, Pagidas K, Ahmed NS, Karri S, Gunn DD, Hurd WW and Singh KK: Mitochondria in ovarian aging and reproductive longevity. Ageing Res Rev. 63:1011682020. View Article : Google Scholar : PubMed/NCBI

346 

Li H, Slone J, Fei L and Huang T: Mitochondrial DNA variants and common diseases: A mathematical model for the diversity of age-related mtDNA mutations. Cells. 8:6082019. View Article : Google Scholar :

347 

Nissanka N and Moraes CT: Mitochondrial DNA heteroplasmy in disease and targeted nuclease-based therapeutic approaches. EMBO Rep. 21:e496122020. View Article : Google Scholar : PubMed/NCBI

348 

West AP and Shadel GS: Mitochondrial DNA in innate immune responses and inflammatory pathology. Nat Rev Immunol. 17:363–375. 2017. View Article : Google Scholar : PubMed/NCBI

349 

Asfaram S, Fakhar M, Mohebali M, Ziaei Hezarjaribi H, Mardani A, Ghezelbash B, Akhoundi B, Zarei Z and Moazeni M: A convenient and sensitive kDNA-PCR for screening of leishmania infantum latent infection among blood donors in a highly endemic focus, northwestern Iran. Acta Parasitol. 67:842–850. 2022. View Article : Google Scholar : PubMed/NCBI

350 

Semerikov VL, Semerikova SA, Khrunyk YY and Putintseva YA: Sequence capture of mitochondrial genome with PCR-generated baits provides new insights into the biogeography of the genus abies mill. Plants (Basel). 11. pp. 7622022, View Article : Google Scholar

351 

Tay E, Chen SC, Green W, Lopez R and Halliday CL: Development of a real-time PCR assay to identify and distinguish between cryptococcus neoformans and cryptococcus gattii species complexes. J Fungi (Basel). 8:4622022. View Article : Google Scholar

352 

Wang J, Balciuniene J, Diaz-Miranda MA, McCormick EM, Aref-Eshghi E, Muir AM, Cao K, Troiani J, Moseley A, Fan Z, et al: Advanced approach for comprehensive mtDNA genome testing in mitochondrial disease. Mol Genet Metab. 135:93–101. 2022. View Article : Google Scholar : PubMed/NCBI

353 

Yang Z, Slone J and Huang T: Next-generation sequencing to characterize mitochondrial genomic DNA heteroplasmy. Curr Protoc. 2:e4122022. View Article : Google Scholar : PubMed/NCBI

354 

Allouche J, Rachmin I, Adhikari K, Pardo LM, Lee JH, McConnell AM, Kato S, Fan S, Kawakami A, Suita Y, et al: NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism. Cell. 184:4268–4283.e20. 2021. View Article : Google Scholar : PubMed/NCBI

355 

Cornman RS, McKenna JE Jr and Fike JA: Composition and distribution of fish environmental DNA in an adirondack watershed. PeerJ. 9:e105392021. View Article : Google Scholar : PubMed/NCBI

356 

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, Abeliovich H, Abildgaard MH, Abudu YP, Acevedo-Arozena A, et al: Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1. Autophagy. 17:1–382. 2021. View Article : Google Scholar : PubMed/NCBI

357 

Matsui H, Ito J, Matsui N, Uechi T, Onodera O and Kakita A: Cytosolic dsDNA of mitochondrial origin induces cytotoxicity and neurodegeneration in cellular and zebrafish models of Parkinson's disease. Nat Commun. 12:31012021. View Article : Google Scholar : PubMed/NCBI

358 

Rhie A, McCarthy SA, Fedrigo O, Damas J, Formenti G, Koren S, Uliano-Silva M, Chow W, Fungtammasan A, Kim J, et al: Towards complete and error-free genome assemblies of all vertebrate species. Nature. 592:737–746. 2021. View Article : Google Scholar : PubMed/NCBI

359 

Rossmann MP, Hoi K, Chan V, Abraham BJ, Yang S, Mullahoo J, Papanastasiou M, Wang Y, Elia I, Perlin JR, et al: Cell-specific transcriptional control of mitochondrial metabolism by TIF1γ drives erythropoiesis. Science. 372:716–721. 2021. View Article : Google Scholar : PubMed/NCBI

360 

Wiessner M, Maroofian R, Ni MY, Pedroni A, Müller JS, Stucka R, Beetz C, Efthymiou S, Santorelli FM, Alfares AA, et al: Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia. Brain. 144:1422–1434. 2021. View Article : Google Scholar : PubMed/NCBI

361 

Wong HH, Seet SH, Maier M, Gurel A, Traspas RM, Lee C, Zhang S, Talim B, Loh AYT, Chia CY, et al: Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy. Am J Hum Genet. 108:1301–1317. 2021. View Article : Google Scholar : PubMed/NCBI

362 

Zhang DG, Zhao T, Hogstrand C, Ye HM, Xu XJ and Luo Z: Oxidized fish oils increased lipid deposition via oxidative stress-mediated mitochondrial dysfunction and the CREB1-Bcl2-Beclin1 pathway in the liver tissues and hepatocytes of yellow catfish. Food Chem. 360:1298142021. View Article : Google Scholar : PubMed/NCBI

363 

Borsche M, König IR, Delcambre S, Petrucci S, Balck A, Brüggemann N, Zimprich A, Wasner K, Pereira SL, Avenali M, et al: Mitochondrial damage-associated inflammation highlights biomarkers in PRKN/PINK1 parkinsonism. Brain. 143:3041–3051. 2020. View Article : Google Scholar : PubMed/NCBI

364 

Fernström J, Ohlsson L, Asp M, Lavant E, Holck A, Grudet C, Westrin Å and Lindqvist D: Plasma circulating cell-free mitochondrial DNA in depressive disorders. PLoS One. 16:e02595912021. View Article : Google Scholar : PubMed/NCBI

365 

Gonçalves VF, Mendes-Silva AP, Koyama E, Vieira E, Kennedy JL and Diniz B: Increased levels of circulating cell-free mtDNA in plasma of late life depression subjects. J Psychiatr Res. 139:25–29. 2021. View Article : Google Scholar : PubMed/NCBI

366 

Liu Y, Zhou K, Guo S, Wang Y, Ji X, Yuan Q, Su L, Guo X, Gu X and Xing J: NGS-based accurate and efficient detection of circulating cell-free mitochondrial DNA in cancer patients. Mol Ther Nucleic Acids. 23:657–666. 2021. View Article : Google Scholar : PubMed/NCBI

367 

Maresca A, Del Dotto V, Romagnoli M, La Morgia C, Di Vito L, Capristo M, Valentino ML and Carelli V; ER-MITO Study Group: Expanding and validating the biomarkers for mitochondrial diseases. J Mol Med (Berl). 98:1467–1478. 2020. View Article : Google Scholar

368 

Nie S, Lu J, Wang L and Gao M: Pro-inflammatory role of cell-free mitochondrial DNA in cardiovascular diseases. IUBMB Life. 72:1879–1890. 2020. View Article : Google Scholar : PubMed/NCBI

369 

Valenti D, Vacca RA, Moro L and Atlante A: Mitochondria can cross cell boundaries: An overview of the biological relevance, pathophysiological implications and therapeutic perspectives of intercellular mitochondrial transfer. Int J Mol Sci. 22:83122021. View Article : Google Scholar : PubMed/NCBI

370 

Zhong XY, Guo Y and Fan Z: Increased level of free-circulating MtDNA in maintenance hemodialysis patients: Possible role in systemic inflammation. J Clin Lab Anal. 36:e245582022. View Article : Google Scholar : PubMed/NCBI

371 

Zhou G, Li Y, Li S, Liu H, Xu F, Lai X, Zhang Q, Xu J and Wan S: Circulating cell-free mtDNA content as a non-invasive prognostic biomarker in HCC patients receiving TACE and traditional Chinese medicine. Front Genet. 12:7194512021. View Article : Google Scholar : PubMed/NCBI

372 

Angelova PR, Andruska KM, Midei MG, Barilani M, Atwal P, Tucher O, Milner P, Heerinckx F and Shchepinov MS: RT001 in progressive supranuclear palsy-clinical and in-vitro observations. Antioxidants (Basel). 10. pp. 10212021, View Article : Google Scholar

373 

Bjørklund G, Tinkov AA, Hosnedlová B, Kizek R, Ajsuvakova OP, Chirumbolo S, Skalnaya MG, Peana M, Dadar M, El-Ansary A, et al: The role of glutathione redox imbalance in autism spectrum disorder: A review. Free Radic Biol Med. 160:149–162. 2020. View Article : Google Scholar : PubMed/NCBI

374 

Blotto BL, Lyra ML, Cardoso MCS, Trefaut Rodrigues M, R Dias I, Marciano-Jr E, Dal Vechio F, Orrico VGD, Brandão RA, Lopes de Assis C, et al: The phylogeny of the casque-headed treefrogs (Hylidae: Hylinae: Lophyohylini). Cladistics. 37:36–72. 2021. View Article : Google Scholar : PubMed/NCBI

375 

Langton AK, Ayer J, Griffiths TW, Rashdan E, Naidoo K, Caley MP, Birch-Machin MA, O'Toole EA, Watson REB and Griffiths CEM: Distinctive clinical and histological characteristics of atrophic and hypertrophic facial photoageing. J Eur Acad Dermatol Venereol. 35:762–768. 2021. View Article : Google Scholar :

376 

Luo ZL, Sun HY, Wu XB, Cheng L and Ren JD: Epigallocatechin-3-gallate attenuates acute pancreatitis induced lung injury by targeting mitochondrial reactive oxygen species triggered NLRP3 inflammasome activation. Food Funct. 12:5658–5667. 2021. View Article : Google Scholar : PubMed/NCBI

377 

Rebelo AP, Eidhof I, Cintra VP, Guillot-Noel L, Pereira CV, Timmann D, Traschütz A, Schöls L, Coarelli G, Durr A, et al: Biallelic loss-of-function variations in PRDX3 cause cerebellar ataxia. Brain. 144:1467–1481. 2021. View Article : Google Scholar : PubMed/NCBI

378 

Wu HC, Rérolle D, Berthier C, Hleihel R, Sakamoto T, Quentin S, Benhenda S, Morganti C, Wu C, Conte L, et al: Actinomycin D targets NPM1c-primed mitochondria to restore PML-driven senescence in AML therapy. Cancer Discov. 11:3198–3213. 2021. View Article : Google Scholar : PubMed/NCBI

379 

Feng B, Wang K, Liu J, Mao G, Cui J, Xuan X, Jiang K and Zhang H: Ultrasensitive apurinic/apyrimidinic site-specific ratio fluorescent rotor for real-time highly selective evaluation of mtDNA oxidative damage in living cells. Anal Chem. 91:13962–13969. 2019. View Article : Google Scholar : PubMed/NCBI

380 

Dabravolski SA, Nikiforov NG, Zhuravlev AD, Orekhov NA, Grechko AV and Orekhov AN: Role of the mtDNA mutations and mitophagy in inflammaging. Int J Mol Sci. 23:13232022. View Article : Google Scholar : PubMed/NCBI

381 

Hamel Y, Mauvais FX, Madrange M, Renard P, Lebreton C, Nemazanyy I, Pellé O, Goudin N, Tang X, Rodero MP, et al: Compromised mitochondrial quality control triggers lipin1-related rhabdomyolysis. Cell Rep Med. 2:1003702021. View Article : Google Scholar : PubMed/NCBI

382 

Karshovska E, Wei Y, Subramanian P, Mohibullah R, Geißler C, Baatsch I, Popal A, Corbalán Campos J, Exner N and Schober A: HIF-1α (hypoxia-inducible factor-1α) promotes macrophage necroptosis by regulating miR-210 and miR-383. Arterioscler Thromb Vasc Biol. 40:583–596. 2020. View Article : Google Scholar : PubMed/NCBI

383 

Gao F, Li L, Fan J, Cao J, Li Y, Chen L and Peng X: An off-on two-photon carbazole-based fluorescent probe: Highly targeting and super-resolution imaging of mtDNA. Anal Chem. 91:3336–3341. 2019. View Article : Google Scholar : PubMed/NCBI

384 

Grady JP, Pickett SJ, Ng YS, Alston CL, Blakely EL, Hardy SA, Feeney CL, Bright AA, Schaefer AM, Gorman GS, et al: mtDNA heteroplasmy level and copy number indicate disease burden in m.3243A>G mitochondrial disease. EMBO Mol Med. 10:e82622018. View Article : Google Scholar :

385 

Bozi LHM, Campos JC, Zambelli VO, Ferreira ND and Ferreira JCB: Mitochondrially-targeted treatment strategies. Mol Aspects Med. 71:1008362020. View Article : Google Scholar

386 

Jing X, Yang F, Shao C, Wei K, Xie M, Shen H and Shu Y: Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer. 18:1572019. View Article : Google Scholar : PubMed/NCBI

387 

Amore G, Romagnoli M, Carbonelli M, Barboni P, Carelli V and La Morgia C: Therapeutic options in hereditary optic neuropathies. Drugs. 81:57–86. 2021. View Article : Google Scholar :

388 

Chen JJ and Bhatti MT: Gene therapy for leber hereditary optic neuropathy: Is vision truly RESCUED? Ophthalmology. 128:661–662. 2021. View Article : Google Scholar : PubMed/NCBI

389 

Mejia-Vergara AJ, Seleme N, Sadun AA and Karanjia R: Pathophysiology of conversion to symptomatic leber hereditary optic neuropathy and therapeutic implications: A review. Curr Neurol Neurosci Rep. 20:112020. View Article : Google Scholar : PubMed/NCBI

390 

Newman NJ, Yu-Wai-Man P, Carelli V, Moster ML, Biousse V, Vignal-Clermont C, Sergott RC, Klopstock T, Sadun AA, Barboni P, et al: Efficacy and safety of intravitreal gene therapy for leber hereditary optic neuropathy treated within 6 months of disease onset. Ophthalmology. 128:649–660. 2021. View Article : Google Scholar : PubMed/NCBI

391 

Stenton SL, Sheremet NL, Catarino CB, Andreeva NA, Assouline Z, Barboni P, Barel O, Berutti R, Bychkov I, Caporali L, et al: Impaired complex I repair causes recessive leber's hereditary optic neuropathy. J Clin Invest. 131:e1382672021. View Article : Google Scholar

392 

Wang L, Ding H, Chen BT, Fan K, Tian Q, Long M, Liang M, Shi D, Yu C and Qin W: Occult primary white matter impairment in leber hereditary optic neuropathy. Eur J Neurol. 28:2871–2881. 2021. View Article : Google Scholar : PubMed/NCBI

393 

Yu-Wai-Man P, Newman NJ, Carelli V, Moster ML, Biousse V, Sadun AA, Klopstock T, Vignal-Clermont C, Sergott RC, Rudolph G, et al: Bilateral visual improvement with unilateral gene therapy injection for leber hereditary optic neuropathy. Sci Transl Med. 12:eaaz74232020. View Article : Google Scholar : PubMed/NCBI

394 

Heighton JN, Brady LI, Sadikovic B, Bulman DE and Tarnopolsky MA: Genotypes of chronic progressive external ophthalmoplegia in a large adult-onset cohort. Mitochondrion. 49:227–231. 2019. View Article : Google Scholar : PubMed/NCBI

395 

Wu Y, Kang L, Wu HL, Hou Y and Wang ZX: Optical coherence tomography findings in chronic progressive external ophthalmoplegia. Chin Med J (Engl). 132:1202–1207. 2019. View Article : Google Scholar

396 

Del Monte F, Angelini F, Villar AM and Gabbarini F: The arrhythmic risk in Kearns-Sayre syndrome: Still many questions unanswered. Europace. 23:980–981. 2021. View Article : Google Scholar : PubMed/NCBI

397 

Di Mambro C, Tamborrino PP and Drago F: The arrhythmic risk in Kearns-Sayre syndrome: Still many questions unanswered-Authors' reply. Europace. 23:981–982. 2021. View Article : Google Scholar : PubMed/NCBI

398 

Di Nora C, Paldino A, Miani D, Finato N, Pizzolitto S, De Maglio G, Vendramin I, Sponga S, Nalli C, Sinagra G and Livi U: Heart transplantation in Kearns-Sayre syndrome. Transplantation. 103:e393–e394. 2019. View Article : Google Scholar : PubMed/NCBI

399 

Nguyen MTB, Micieli J and Margolin E: Teaching neuroImages: Kearns-Sayre syndrome. Neurology. 92:e519–e520. 2019. View Article : Google Scholar : PubMed/NCBI

400 

Ashton TM, McKenna WG, Kunz-Schughart LA and Higgins GS: Oxidative phosphorylation as an emerging target in cancer therapy. Clin Cancer Res. 24:2482–2490. 2018. View Article : Google Scholar : PubMed/NCBI

401 

Bonora M, Wieckowski MR, Sinclair DA, Kroemer G, Pinton P and Galluzzi L: Targeting mitochondria for cardiovascular disorders: Therapeutic potential and obstacles. Nat Rev Cardiol. 16:33–55. 2019. View Article : Google Scholar :

402 

Ni K, Lan G, Veroneau SS, Duan X, Song Y and Lin W: Nanoscale metal-organic frameworks for mitochondria-targeted radiotherapy-radiodynamic therapy. Nat Commun. 9:43212018. View Article : Google Scholar : PubMed/NCBI

403 

Porporato PE, Filigheddu N, Pedro JMB, Kroemer G and Galluzzi L: Mitochondrial metabolism and cancer. Cell Res. 28:265–280. 2018. View Article : Google Scholar :

404 

Qi T, Chen B, Wang Z, Du H, Liu D, Yin Q, Liu B, Zhang Q and Wang Y: A pH-activatable nanoparticle for dual-stage precisely mitochondria-targeted photodynamic anticancer therapy. Biomaterials. 213:1192192019. View Article : Google Scholar : PubMed/NCBI

405 

Ramachandra CJA, Hernandez-Resendiz S, Crespo-Avilan GE, Lin YH and Hausenloy DJ: Mitochondria in acute myocardial infarction and cardioprotection. EBioMedicine. 57:1028842020. View Article : Google Scholar : PubMed/NCBI

406 

Soukas AA, Hao H and Wu L: Metformin as anti-aging therapy: Is it for everyone? Trends Endocrinol Metab. 30:745–755. 2019. View Article : Google Scholar : PubMed/NCBI

407 

Bonora E, Chakrabarty S, Kellaris G, Tsutsumi M, Bianco F, Bergamini C, Ullah F, Isidori F, Liparulo I, Diquigiovanni C, et al: Biallelic variants in LIG3 cause a novel mitochondrial neurogastrointestinal encephalomyopathy. Brain. 144:1451–1466. 2021. View Article : Google Scholar : PubMed/NCBI

408 

D'Angelo R, Boschetti E, Amore G, Costa R, Pugliese A, Caporali L, Gramegna LL, Papa V, Vizioli L, Capristo M, et al: Liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Clinical long-term follow-up and pathogenic implications. J Neurol. 267:3702–3710. 2020. View Article : Google Scholar : PubMed/NCBI

409 

Hirano M, Carelli V, De Giorgio R, Pironi L, Accarino A, Cenacchi G, D'Alessandro R, Filosto M, Martí R, Nonino F, et al: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE international network. J Inherit Metab Dis. 44:376–387. 2021. View Article : Google Scholar :

410 

Kripps K, Nakayuenyongsuk W, Shayota BJ, Berquist W, Gomez-Ospina N, Esquivel CO, Concepcion W, Sampson JB, Cristin DJ, Jackson WE, et al: Successful liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Mol Genet Metab. 130:58–64. 2020. View Article : Google Scholar : PubMed/NCBI

411 

Parés M, Fornaguera C, Vila-Julià F, Oh S, Fan SHY, Tam YK, Comes N, Vidal F, Martí R, Borrós S and Barquinero J: Preclinical assessment of a gene-editing approach in a mouse model of mitochondrial neurogastrointestinal encephalomyopathy. Hum Gene Ther. 32:1210–1223. 2021. View Article : Google Scholar : PubMed/NCBI

412 

Jackson CB, Turnbull DM, Minczuk M and Gammage PA: Therapeutic manipulation of mtDNA heteroplasmy: A shifting perspective. Trends Mol Med. 26:698–709. 2020. View Article : Google Scholar : PubMed/NCBI

413 

Jiang Z and Shen H: Mitochondria: Emerging therapeutic strategies for oocyte rescue. Reprod Sci. 29:711–722. 2022. View Article : Google Scholar

414 

Mok BY, de Moraes MH, Zeng J, Bosch DE, Kotrys AV, Raguram A, Hsu F, Radey MC, Peterson SB, Mootha VK, et al: A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing. Nature. 583:631–637. 2020. View Article : Google Scholar : PubMed/NCBI

415 

Ng YS, Bindoff LA, Gorman GS, Klopstock T, Kornblum C, Mancuso M, McFarland R, Sue C M, Suomalainen A, Taylor RW, et al: Mitochondrial disease in adults: Recent advances and future promise. Lancet Neurol. 20:573–584. 2021. View Article : Google Scholar : PubMed/NCBI

416 

Fang H, Yao S, Chen Q, Liu C, Cai Y, Geng S, Bai Y, Tian Z, Zacharias AL, Takebe T, et al: De novo-designed near-infrared nanoaggregates for super-resolution monitoring of lysosomes in cells, in whole organoids, and in vivo. ACS Nano. 13:14426–14436. 2019. View Article : Google Scholar : PubMed/NCBI

417 

Gong X, Pu X, Wang J, Yang L, Cui Y, Li L, Sun X, Liu J, Bai J and Wang Y: Enhancing of nanocatalyst-driven chemodynaminc therapy for endometrial cancer cells through inhibition of PINK1/parkin-mediated mitophagy. Int J Nanomedicine. 16:6661–6679. 2021. View Article : Google Scholar : PubMed/NCBI

418 

González LF, Bevilacqua LE and Naves R: Nanotechnology-based drug delivery strategies to repair the mitochondrial function in neuroinflammatory and neurodegenerative diseases. Pharmaceutics. 13:20552021. View Article : Google Scholar : PubMed/NCBI

419 

Gu X, Kwok RTK, Lam JWY and Tang BZ: AIEgens for biological process monitoring and disease theranostics. Biomaterials. 146:115–135. 2017. View Article : Google Scholar : PubMed/NCBI

420 

He C, Jiang S, Yao H, Zhang L, Yang C, Jiang S, Ruan F, Zhan D, Liu G, Lin Z, et al: High-content analysis for mitophagy response to nanoparticles: A potential sensitive biomarker for nanosafety assessment. Nanomedicine. 15:59–69. 2019. View Article : Google Scholar

421 

He G, Pan X, Liu X, Zhu Y, Ma Y, Du C, Liu X and Mao C: HIF-1α-mediated mitophagy determines ZnO nanoparticle-induced human osteosarcoma cell death both in vitro and in vivo. ACS Appl Mater Interfaces. 12:48296–48309. 2020. View Article : Google Scholar : PubMed/NCBI

422 

Zhao M, Liu S, Wang C, Wang Y, Wan M, Liu F, Gong M, Yuan Y, Chen Y, Cheng J, et al: Mesenchymal stem cell-derived extracellular vesicles attenuate mitochondrial damage and inflammation by stabilizing mitochondrial DNA. ACS Nano. 15:1519–1538. 2021. View Article : Google Scholar

423 

Macdonald R, Barnes K, Hastings C and Mortiboys H: Mitochondrial abnormalities in Parkinson's disease and Alzheimer's disease: Can mitochondria be targeted therapeutically? Biochem Soc Trans. 46:891–909. 2018. View Article : Google Scholar : PubMed/NCBI

424 

Tan DX, Manchester LC, Liu X, Rosales-Corral SA, Acuna-Castroviejo D and Reiter RJ: Mitochondria and chloroplasts as the original sites of melatonin synthesis: A hypothesis related to melatonin's primary function and evolution in eukaryotes. J Pineal Res. 54:127–138. 2013. View Article : Google Scholar

425 

Lee JH, Park A, Oh KJ, Lee SC, Kim WK and Bae KH: The role of adipose tissue mitochondria: Regulation of mitochondrial function for the treatment of metabolic diseases. Int J Mol Sci. 20:49242019. View Article : Google Scholar :

426 

Wallace DC: Mitochondrial genetic medicine. Nat Genet. 50:1642–1649. 2018. View Article : Google Scholar : PubMed/NCBI

427 

Strobbe D and Campanella M: Anxiolytic therapy: A paradigm of successful mitochondrial pharmacology. Trends Pharmacol Sci. 39:437–439. 2018. View Article : Google Scholar : PubMed/NCBI

428 

Wang XQ, Peng M, Li CX, Zhang Y, Zhang M, Tang Y, Liu MD, Xie BR and Zhang XZ: Real-time imaging of free radicals for mitochondria-targeting hypoxic tumor therapy. Nano Lett. 18:6804–6811. 2018. View Article : Google Scholar : PubMed/NCBI

429 

Kim HK, Noh YH, Nilius B, Ko KS, Rhee BD, Kim N and Han J: Current and upcoming mitochondrial targets for cancer therapy. Semin Cancer Biol. 47:154–167. 2017. View Article : Google Scholar : PubMed/NCBI

430 

Lleonart ME, Grodzicki R, Graifer DM and Lyakhovich A: Mitochondrial dysfunction and potential anticancer therapy. Med Res Rev. 37:1275–1298. 2017. View Article : Google Scholar : PubMed/NCBI

431 

Tian J, Huang B, Cui Z, Wang P, Chen S, Yang G and Zhang W: Mitochondria-targeting and ROS-sensitive smart nanoscale supramolecular organic framework for combinational amplified photodynamic therapy and chemotherapy. Acta Biomater. 130:447–459. 2021. View Article : Google Scholar : PubMed/NCBI

432 

Kim HJ, Maiti P and Barrientos A: Mitochondrial ribosomes in cancer. Semin Cancer Biol. 47:67–81. 2017. View Article : Google Scholar : PubMed/NCBI

433 

Chen WW, Freinkman E and Sabatini DM: Rapid immunopurification of mitochondria for metabolite profiling and absolute quantification of matrix metabolites. Nat Protoc. 12:2215–2231. 2017. View Article : Google Scholar

434 

Jung HS, Lee JH, Kim K, Koo S, Verwilst P, Sessler JL, Kang C and Kim JS: A mitochondria-targeted cryptocyanine-based photothermogenic photosensitizer. J Am Chem Soc. 139:9972–9978. 2017. View Article : Google Scholar : PubMed/NCBI

435 

Roth KG, Mambetsariev I, Kulkarni P and Salgia R: The mitochondrion as an emerging therapeutic target in cancer. Trends Mol Med. 26:119–134. 2020. View Article : Google Scholar :

436 

Nash GT, Luo T, Lan G, Ni K, Kaufmann M and Lin W: Nanoscale metal-organic layer isolates phthalocyanines for efficient mitochondria-targeted photodynamic therapy. J Am Chem Soc. 143:2194–2199. 2021. View Article : Google Scholar : PubMed/NCBI

437 

Russell OM, Gorman GS, Lightowlers RN and Turnbull DM: Mitochondrial diseases: Hope for the future. Cell. 181:168–188. 2020. View Article : Google Scholar : PubMed/NCBI

438 

Saeb-Parsy K, Martin JL, Summers DM, Watson CJE, Krieg T and Murphy MP: Mitochondria as therapeutic targets in transplantation. Trends Mol Med. 27:185–198. 2021. View Article : Google Scholar

439 

Kelly B and Pearce EL: Amino assets: How amino acids support immunity. Cell Metab. 32:154–175. 2020. View Article : Google Scholar : PubMed/NCBI

440 

Rahman J and Rahman S: Mitochondrial medicine in the omics era. Lancet. 391:2560–2574. 2018. View Article : Google Scholar : PubMed/NCBI

441 

Tabish TA and Narayan RJ: Mitochondria-targeted graphene for advanced cancer therapeutics. Acta Biomater. 129:43–56. 2021. View Article : Google Scholar : PubMed/NCBI

442 

Yuan P, Deng FA, Liu YB, Zheng RR, Rao XN, Qiu XZ, Zhang DW, Yu XY, Cheng H and Li SY: Mitochondria targeted O2 economizer to alleviate tumor hypoxia for enhanced photodynamic therapy. Adv Healthc Mater. 10:e21001982021. View Article : Google Scholar

443 

Ballarò R, Lopalco P, Audrito V, Beltrà M, Pin F, Angelini R, Costelli P, Corcelli A, Bonetto A, Szeto HH, et al: Targeting mitochondria by SS-31 ameliorates the whole body energy status in cancer- and chemotherapy-induced cachexia. Cancers (Basel). 13. pp. 8502021, View Article : Google Scholar

444 

Bhatti JS, Tamarai K, Kandimalla R, Manczak M, Yin X, Ramasubramanian B, Sawant N, Pradeepkiran JA, Vijayan M, Kumar S and Reddy PH: Protective effects of a mitochondria-targeted small peptide SS31 against hyperglycemia-induced mitochondrial abnormalities in the liver tissues of diabetic mice, Tallyho/JngJ mice. Mitochondrion. 58:49–58. 2021. View Article : Google Scholar : PubMed/NCBI

445 

Deng HF, Yue LX, Wang NN, Zhou YQ, Zhou W, Liu X, Ni YH, Huang CS, Qiu LZ, Liu H, et al: Mitochondrial iron overload-mediated inhibition of Nrf2-HO-1/GPX4 assisted ALI-induced nephrotoxicity. Front Pharmacol. 11:6245292021. View Article : Google Scholar : PubMed/NCBI

446 

Le Gal K, Wiel C, Ibrahim MX, Henricsson M, Sayin VI and Bergo MO: Mitochondria-targeted antioxidants MitoQ and MitoTEMPO Do not influence BRAF-driven malignant melanoma and KRAS-driven lung cancer progression in mice. Antioxidants (Basel). 10:1632021. View Article : Google Scholar

447 

Bhatti JS, Thamarai K, Kandimalla R, Manczak M, Yin X, Kumar S, Vijayan M and Reddy PH: Mitochondria-targeted small peptide, SS31 ameliorates diabetes induced mitochondrial dynamics in male TallyHO/JngJ mice. Mol Neurobiol. 58:795–808. 2021. View Article : Google Scholar :

448 

Grosser JA, Fehrman RL, Keefe D, Redmon M and Nickells RW: The effects of a mitochondrial targeted peptide (elamipretide/SS31) on BAX recruitment and activation during apoptosis. BMC Res Notes. 14:1982021. View Article : Google Scholar : PubMed/NCBI

449 

He Y, Chen Z, Zhang R, Quan Z, Xu Y, He B and Ren Y: Mitochondrial-targeted antioxidant peptide SS31 prevents RPE cell death under oxidative stress. Biomed Res Int. 2022:61803492022. View Article : Google Scholar : PubMed/NCBI

450 

He Y, Quan Z, Zhang R, He B, Xu Y, Chen Z, Ren Y and Li K: Preparation of targeted mitochondrion nanoscale-release peptides and their efficiency on eukaryotic cells. J Biomed Nanotechnol. 17:1679–1689. 2021. View Article : Google Scholar : PubMed/NCBI

451 

He Y, Zhang R, Quan Z, He B, Xu Y, Chen Z, Ren Y and Liu X: Synthesis, characterization, and specific localization of mitochondrial-targeted antioxidant peptide SS31 probe. Biomed Res Int. 2021:99156992021. View Article : Google Scholar : PubMed/NCBI

452 

Sun M, Ma J, Ye J, Fan H, Le J and Zhu J: Protective effect of mitochondria-targeted antioxidant peptide SS-31 in sepsis-induced acute kidney injury. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 33:1418–1422. 2021.In Chinese.

453 

Zhu Y, Luo M, Bai X, Li J, Nie P, Li B and Luo P: SS-31, a mitochondria-targeting peptide, ameliorates kidney disease. Oxid Med Cell Longev. 2022:12955092022. View Article : Google Scholar : PubMed/NCBI

454 

Olgar Y, Billur D, Tuncay E and Turan B: MitoTEMPO provides an antiarrhythmic effect in aged-rats through attenuation of mitochondrial reactive oxygen species. Exp Gerontol. 136:1109612020. View Article : Google Scholar : PubMed/NCBI

455 

Tuncer S, Akkoca A, Celen MC and Dalkilic N: Can MitoTEMPO protect rat sciatic nerve against ischemia-reperfusion injury? Naunyn Schmiedebergs Arch Pharmacol. 394:545–553. 2021. View Article : Google Scholar : PubMed/NCBI

456 

Vrijsen S, Besora-Casals L, van Veen S, Zielich J, Van den Haute C, Hamouda NN, Fischer C, Ghesquière B, Tournev I, Agostinis P, et al: ATP13A2-mediated endo-lysosomal polyamine export counters mitochondrial oxidative stress. Proc Natl Acad Sci USA. 117:31198–31207. 2020. View Article : Google Scholar : PubMed/NCBI

457 

Wang Y, Zhao Y, Wang Z, Sun R, Zou B, Li R, Liu D, Lin M, Zhou J, Ning S, et al: Peroxiredoxin 3 inhibits acetaminophen-induced liver pyroptosis through the regulation of mitochondrial ROS. Front Immunol. 12:6527822021. View Article : Google Scholar : PubMed/NCBI

458 

Gao J, Zhan J and Yang Z: Enzyme-instructed self-assembly (EISA) and hydrogelation of peptides. Adv Mater. 32:e18057982020. View Article : Google Scholar

459 

Liu C, Liu B, Zhao J, Di Z, Chen D, Gu Z, Li L and Zhao Y: Nd3+-sensitized upconversion metal-organic frameworks for mitochondria-targeted amplified photodynamic therapy. Angew Chem Int Ed Engl. 59:2634–2638. 2020. View Article : Google Scholar

460 

Lu M, Qu A, Li S, Sun M, Xu L, Kuang H and Xu C: Mitochondria-targeting plasmonic spiky nanorods increase the elimination of aging cells in vivo. Angew Chem Int Ed Engl. 59:8698–8705. 2020. View Article : Google Scholar : PubMed/NCBI

461 

Li C, Zhang W, Liu S, Hu X and Xie Z: Mitochondria-targeting organic nanoparticles for enhanced photodynamic/photothermal therapy. ACS Appl Mater Interfaces. 12:30077–30084. 2020. View Article : Google Scholar : PubMed/NCBI

462 

Zhang CX, Cheng Y, Liu DZ, Liu M, Cui H, Zhang BL, Mei QB and Zhou SY: Mitochondria-targeted cyclosporin A delivery system to treat myocardial ischemia reperfusion injury of rats. J Nanobiotechnology. 17:182019. View Article : Google Scholar : PubMed/NCBI

463 

Sun J, Zhang J, Tian J, Virzì GM, Digvijay K, Cueto L, Yin Y, Rosner MH and Ronco C: Mitochondria in sepsis-induced AKI. J Am Soc Nephrol. 30:1151–1161. 2019. View Article : Google Scholar : PubMed/NCBI

464 

Yang G, Chen C, Zhu Y, Liu Z, Xue Y, Zhong S, Wang C, Gao Y and Zhang W: GSH-activatable NIR nanoplatform with mitochondria targeting for enhancing tumor-specific therapy. ACS Appl Mater Interfaces. 11:44961–44969. 2019. View Article : Google Scholar : PubMed/NCBI

465 

Gabandé-Rodríguez E, Gómez de Las Heras MM and Mittelbrunn M: Control of inflammation by calorie restriction mimetics: On the crossroad of autophagy and mitochondria. Cells. 9:822019. View Article : Google Scholar

466 

Cho H, Cho YY, Shim MS, Lee JY, Lee HS and Kang HC: Mitochondria-targeted drug delivery in cancers. Biochim Biophys Acta Mol Basis Dis. 1866:1658082020. View Article : Google Scholar : PubMed/NCBI

467 

Liu K, Zhou Z, Pan M and Zhang L: Stem cell-derived mitochondria transplantation: A promising therapy for mitochondrial encephalomyopathy. CNS Neurosci Ther. 27:733–742. 2021. View Article : Google Scholar : PubMed/NCBI

468 

Deng Y, Jia F, Chen X, Jin Q and Ji J: ATP suppression by pH-activated mitochondria-targeted delivery of nitric oxide nanoplatform for drug resistance reversal and metastasis inhibition. Small. 16:e20017472020. View Article : Google Scholar : PubMed/NCBI

469 

Gao C, Wang Y, Sun J, Han Y, Gong W, Li Y, Feng Y, Wang H, Yang M, Li Z, et al: Neuronal mitochondria-targeted delivery of curcumin by biomimetic engineered nanosystems in Alzheimer's disease mice. Acta Biomater. 108:285–299. 2020. View Article : Google Scholar : PubMed/NCBI

470 

Andrieux P, Chevillard C, Cunha-Neto E and Nunes JPS: Mitochondria as a cellular hub in infection and inflammation. Int J Mol Sci. 22:113382021. View Article : Google Scholar : PubMed/NCBI

471 

Zeng WN, Yu QP, Wang D, Liu JL, Yang QJ, Zhou ZK and Zeng YP: Mitochondria-targeting graphene oxide nanocomposites for fluorescence imaging-guided synergistic phototherapy of drug-resistant osteosarcoma. J Nanobiotechnology. 19:792021. View Article : Google Scholar : PubMed/NCBI

472 

Nam HY, Hong JA, Choi J, Shin S, Cho SK, Seo J and Lee J: Mitochondria-targeting peptoids. Bioconjug Chem. 29:1669–1676. 2018. View Article : Google Scholar : PubMed/NCBI

473 

El-Hattab AW, Zarante AM, Almannai M and Scaglia F: Therapies for mitochondrial diseases and current clinical trials. Mol Genet Metab. 122:1–9. 2017. View Article : Google Scholar : PubMed/NCBI

474 

Han Y, Chu X, Cui L, Fu S, Gao C, Li Y and Sun B: Neuronal mitochondria-targeted therapy for Alzheimer's disease by systemic delivery of resveratrol using dual-modified novel biomimetic nanosystems. Drug Deliv. 27:502–518. 2020. View Article : Google Scholar : PubMed/NCBI

475 

Mohammadinejad R, Moosavi MA, Tavakol S, Vardar DÖ, Hosseini A, Rahmati M, Dini L, Hussain S, Mandegary A and Klionsky DJ: Necrotic, apoptotic and autophagic cell fates triggered by nanoparticles. Autophagy. 15:4–33. 2019. View Article : Google Scholar

476 

Vincent AE, Turnbull DM, Eisner V, Hajnóczky G and Picard M: Mitochondrial nanotunnels. Trends Cell Biol. 27:787–799. 2017. View Article : Google Scholar : PubMed/NCBI

477 

Wu T, Liang X, Liu X, Li Y, Wang Y, Kong L and Tang M: Induction of ferroptosis in response to graphene quantum dots through mitochondrial oxidative stress in microglia. Part Fibre Toxicol. 17:302020. View Article : Google Scholar : PubMed/NCBI

478 

Wang H, Shi W, Zeng D, Huang Q, Xie J, Wen H, Li J, Yu X, Qin L and Zhou Y: pH-activated, mitochondria-targeted, and redox-responsive delivery of paclitaxel nanomicelles to overcome drug resistance and suppress metastasis in lung cancer. J Nanobiotechnology. 19:1522021. View Article : Google Scholar : PubMed/NCBI

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October-2022
Volume 50 Issue 4

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Yin Y and Yin Y: Common methods in mitochondrial research (Review). Int J Mol Med 50: 126, 2022
APA
Yin, Y., & Yin, Y. (2022). Common methods in mitochondrial research (Review). International Journal of Molecular Medicine, 50, 126. https://doi.org/10.3892/ijmm.2022.5182
MLA
Yin, Y., Shen, H."Common methods in mitochondrial research (Review)". International Journal of Molecular Medicine 50.4 (2022): 126.
Chicago
Yin, Y., Shen, H."Common methods in mitochondrial research (Review)". International Journal of Molecular Medicine 50, no. 4 (2022): 126. https://doi.org/10.3892/ijmm.2022.5182