
Mitochondrial calcium uniporter complex: An emerging therapeutic target for cardiovascular diseases (Review)
- Authors:
- Yaling Li
- Hongmin Hu
- Chun Chu
- Jun Yang
-
Affiliations: Department of Cardiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421000, P.R. China, Department of Pharmacy, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421000, P.R. China - Published online on: December 31, 2024 https://doi.org/10.3892/ijmm.2024.5481
- Article Number: 40
-
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
![]() |
![]() |
Joseph P, Leong D, McKee M, Anand SS, Schwalm JD, Teo K, Mente A and Yusuf S: Reducing the global burden of cardiovascular disease, part 1: The epidemiology and risk factors. Circ Res. 121:677–694. 2017. View Article : Google Scholar : PubMed/NCBI | |
Ras J, Smith DL, Kengne AP, Soteriades EE and Leach L: Cardiovascular disease risk factors, musculoskeletal health, physical fitness, and occupational performance in firefighters: A narrative review. J Environ Public Health. 2022:73464082022. View Article : Google Scholar : PubMed/NCBI | |
Li Q, Zhang S, Yang G, Wang X, Liu F, Li Y, Chen Y, Zhou T, Xie D, Liu Y and Zhang L: Energy metabolism: A critical target of cardiovascular injury. Biomed Pharmacother. 165:1152712023. View Article : Google Scholar : PubMed/NCBI | |
Liang S, Yegambaram M, Wang T, Wang J, Black SM and Tang H: Mitochondrial metabolism, redox, and calcium homeostasis in pulmonary arterial hypertension. Biomedicines. 10:3412022. View Article : Google Scholar : PubMed/NCBI | |
Varghese E, Samuel SM, Sadiq Z, Kubatka P, Liskova A, Benacka J, Pazinka P, Kruzliak P and Büsselberg D: Anti-Cancer agents in proliferation and cell death: The calcium connection. Int J Mol Sci. 20:30172019. View Article : Google Scholar : PubMed/NCBI | |
Sukumaran P, Nascimento Da Conceicao V, Sun Y, Ahamad N, Saraiva LR, Selvaraj S and Singh BB: Calcium Signaling Regulates Autophagy and Apoptosis. Cells. 10:21252021. View Article : Google Scholar : PubMed/NCBI | |
Reyes Gaido OE, Nkashama LJ, Schole KL, Wang Q, Umapathi P, Mesubi OO, Konstantinidis K, Luczak ED and Anderson ME: CaMKII as a therapeutic target in cardiovascular disease. Annu Rev Pharmacol Toxicol. 63:249–272. 2023. View Article : Google Scholar | |
Viola HM and Hool LC: Targeting calcium and the mitochondria in prevention of pathology in the heart. Curr Drug Targets. 12:748–760. 2011. View Article : Google Scholar : PubMed/NCBI | |
Fearnley CJ, Roderick HL and Bootman MD: Calcium signaling in cardiac myocytes. Cold Spring Harb Perspect Biol. 3:a0042422011. View Article : Google Scholar : PubMed/NCBI | |
Matchkov VV, Kudryavtseva O and Aalkjaer C: Intracellular Ca(2)(+) signalling and phenotype of vascular smooth muscle cells. Basic Clin Pharmacol Toxicol. 110:42–48. 2012. View Article : Google Scholar | |
Beghi S, Furmanik M, Jaminon A, Veltrop R, Rapp N, Wichapong K, Bidar E, Buschini A and Schurgers LJ: Calcium signalling in heart and vessels: Role of calmodulin and downstream calmodulin-dependent protein kinases. Int J Mol Sci. 23:161392022. View Article : Google Scholar : PubMed/NCBI | |
Kamer KJ and Mootha VK: The molecular era of the mitochondrial calcium uniporter. Nat Rev Mol Cell Biol. 16:545–553. 2015. View Article : Google Scholar : PubMed/NCBI | |
D'Angelo D and Rizzuto R: The mitochondrial calcium uniporter (MCU): Molecular identity and role in human diseases. Biomolecules. 13:13042023. View Article : Google Scholar : PubMed/NCBI | |
Lim D, Dematteis G, Tapella L, Genazzani AA, Calì T, Brini M and Verkhratsky A: Ca(2+) handling at the mitochondria-ER contact sites in neurodegeneration. Cell Calcium. 98:1024532021. View Article : Google Scholar : PubMed/NCBI | |
De Stefani D, Patron M and Rizzuto R: Structure and function of the mitochondrial calcium uniporter complex. Biochim Biophys Acta. 1853:2006–2011. 2015. View Article : Google Scholar : PubMed/NCBI | |
Nemani N, Shanmughapriya S and Madesh M: Molecular regulation of MCU: Implications in physiology and disease. Cell Calcium. 74:86–93. 2018. View Article : Google Scholar : PubMed/NCBI | |
Fieni F, Lee SB, Jan YN and Kirichok Y: Activity of the mitochondrial calcium uniporter varies greatly between tissues. Nat Commun. 3:13172012. View Article : Google Scholar : PubMed/NCBI | |
Murphy E and Liu JC: Mitochondrial calcium and reactive oxygen species in cardiovascular disease. Cardiovasc Res. 119:1105–1116. 2023. View Article : Google Scholar : | |
Meinild Lundby AK, Jacobs RA, Gehrig S, de Leur J, Hauser M, Bonne TC, Flück D, Dandanell S, Kirk N, Kaech A, et al: Exercise training increases skeletal muscle mitochondrial volume density by enlargement of existing mitochondria and not de novo biogenesis. Acta Physiol (Oxf). 222:2018. View Article : Google Scholar | |
Kim HK, Kang YG, Jeong SH, Park N, Marquez J, Ko KS, Rhee BD, Shin JW and Han J: Cyclic stretch increases mitochondrial biogenesis in a cardiac cell line. Biochem Biophys Res Commun. 505:768–774. 2018. View Article : Google Scholar : PubMed/NCBI | |
Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL, et al: Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature. 476:341–345. 2011. View Article : Google Scholar : PubMed/NCBI | |
Baradaran R, Wang C, Siliciano AF and Long SB: Cryo-EM structures of fungal and metazoan mitochondrial calcium uniporters. Nature. 559:580–584. 2018. View Article : Google Scholar : PubMed/NCBI | |
De Stefani D, Raffaello A, Teardo E, Szabo I and Rizzuto R: A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature. 476:336–340. 2011. View Article : Google Scholar : PubMed/NCBI | |
Raffaello A, De Stefani D, Sabbadin D, Teardo E, Merli G, Picard A, Checchetto V, Moro S, Szabò I and Rizzuto R: The mitochondrial calcium uniporter is a multimer that can include a dominant-negative pore-forming subunit. EMBO J. 32:2362–2376. 2013. View Article : Google Scholar : PubMed/NCBI | |
Yoo J, Wu M, Yin Y, Herzik MA Jr, Lander GC and Lee SY: Cryo-EM structure of a mitochondrial calcium uniporter. Science. 361:506–511. 2018. View Article : Google Scholar : PubMed/NCBI | |
Lambert JP, Luongo TS, Tomar D, Jadiya P, Gao E, Zhang X, Lucchese AM, Kolmetzky DW, Shah NS and Elrod W: MCUB regulates the molecular composition of the mitochondrial calcium uniporter channel to limit mitochondrial calcium overload during stress. Circulation. 140:1720–1733. 2019. View Article : Google Scholar : PubMed/NCBI | |
Mammucari C, Raffaello A, Vecellio Reane D, Gherardi G, De Mario A and Rizzuto R: Mitochondrial calcium uptake in organ physiology: From molecular mechanism to animal models. Pflugers Arch. 470:1165–1179. 2018. View Article : Google Scholar : PubMed/NCBI | |
Sancak Y, Markhard AL, Kitami T, Kovács-Bogdán E, Kamer KJ, Udeshi ND, Carr SA, Chaudhuri D, Clapham DE, Li AA, et al: EMRE is an essential component of the mitochondrial calcium uniporter complex. Science. 342:1379–1382. 2013. View Article : Google Scholar : PubMed/NCBI | |
Yamamoto T, Yamagoshi R, Harada K, Kawano M, Minami N, Ido Y, Kuwahara K, Fujita A, Ozono M, Watanabe A, et al: Analysis of the structure and function of EMRE in a yeast expression system. Biochim Biophys Acta. 1857:831–839. 2016. View Article : Google Scholar : PubMed/NCBI | |
Delgado BD and Long SB: Mechanisms of ion selectivity and throughput in the mitochondrial calcium uniporter. Sci Adv. 8:eade15162022. View Article : Google Scholar : PubMed/NCBI | |
Gottschalk B, Klec C, Leitinger G, Bernhart E, Rost R, Bischof H, Madreiter-Sokolowski CT, Radulović S, Eroglu E, Sattler W, et al: MICU1 controls cristae junction and spatially anchors mitochondrial Ca(2+) uniporter complex. Nat Commun. 10:37322019. View Article : Google Scholar : PubMed/NCBI | |
Konig T, Tröder SE, Bakka K, Korwitz A, Richter-Dennerlein R, Lampe PA, Patron M, Mühlmeister M, Guerrero-Castillo S, Brandt U, et al: The m-AAA protease associated with neurodegeneration limits MCU activity in mitochondria. Mol Cell. 64:148–162. 2016. View Article : Google Scholar : PubMed/NCBI | |
Hasan P, Berezhnaya E, Rodríguez-Prados M, Weaver D, Bekeova C, Cartes-Saavedra B, Birch E, Beyer AM, Santos JH, Seifert EL, et al: MICU1 and MICU2 control mitochondrial calcium signaling in the mammalian heart. Proc Natl Acad Sci USA. 121:e24024911212024. View Article : Google Scholar : PubMed/NCBI | |
Plovanich M, Bogorad RL, Sancak Y, Kamer KJ, Strittmatter L, Li AA, Girgis HS, Kuchimanchi S, De Groot J, Speciner L, et al: MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling. PLoS One. 8:e557852013. View Article : Google Scholar : PubMed/NCBI | |
Kamer KJ, Grabarek Z and Mootha VK: High-affinity cooperative Ca(2+) binding by MICU1-MICU2 serves as an on-off switch for the uniporter. EMBO Rep. 18:1397–1411. 2017. View Article : Google Scholar : PubMed/NCBI | |
Patron M, Checchetto V, Raffaello A, Teardo E, Vecellio Reane D, Mantoan M, Granatiero V, Szabò I, De Stefani D and Rizzuto R: MICU1 and MICU2 finely tune the mitochondrial Ca2+ uniporter by exerting opposite effects on MCU activity. Mol Cell. 53:726–737. 2014. View Article : Google Scholar : PubMed/NCBI | |
Patron M, Granatiero V, Espino J, Rizzuto R and De Stefani D: MICU3 is a tissue-specific enhancer of mitochondrial calcium uptake. Cell Death Differ. 26:179–195. 2019. View Article : Google Scholar | |
Tomar D, Dong Z, Shanmughapriya S, Koch DA, Thomas T, Hoffman NE, Timbalia SA, Goldman SJ, Breves SL, Corbally DP, et al: MCUR1 is a scaffold factor for the MCU complex function and promotes mitochondrial bioenergetics. Cell Rep. 15:1673–1685. 2016. View Article : Google Scholar : PubMed/NCBI | |
Mallilankaraman K, Cárdenas C, Doonan PJ, Chandramoorthy HC, Irrinki KM, Golenár T, Csordás G, Madireddi P, Yang J, Müller M, et al: MCUR1 is an essential component of mitochondrial Ca2+ uptake that regulates cellular metabolism. Nat Cell Biol. 14:1336–1343. 2012. View Article : Google Scholar : PubMed/NCBI | |
Zulkifli M, Neff JK, Timbalia SA, Garza NM, Chen Y, Watrous JD, Murgia M, Trivedi PP, Anderson SK, Tomar D, et al: Yeast homologs of human MCUR1 regulate mitochondrial proline metabolism. Nat Commun. 11:48662020. View Article : Google Scholar : PubMed/NCBI | |
Paupe V, Prudent J, Dassa EP, Rendon OZ and Shoubridge EA: CCDC90A (MCUR1) is a cytochrome c oxidase assembly factor and not a regulator of the mitochondrial calcium uniporter. Cell Metab. 21:109–116. 2015. View Article : Google Scholar : PubMed/NCBI | |
Bassi MT, Manzoni M, Bresciani R, Pizzo MT, Della Monica A, Barlati S, Monti E and Borsani G: Cellular expression and alternative splicing of SLC25A23, a member of the mitochondrial Ca2+-dependent solute carrier gene family. Gene. 345:173–182. 2005. View Article : Google Scholar : PubMed/NCBI | |
Hoffman NE, Chandramoorthy HC, Shanmughapriya S, Zhang XQ, Vallem S, Doonan PJ, Malliankaraman K, Guo S, Rajan S, Elrod JW, et al: SLC25A23 augments mitochondrial Ca(2)(+) uptake, interacts with MCU, and induces oxidative stress-mediated cell death. Mol Biol Cell. 25:936–947. 2014. View Article : Google Scholar : PubMed/NCBI | |
Rochette L, Meloux A, Zeller M, Malka G, Cottin Y and Vergely C: Mitochondrial SLC25 carriers: Novel Targets for Cancer Therapy. Molecules. 25:24172020. View Article : Google Scholar : PubMed/NCBI | |
Jennings RB and Reimer KA: The cell biology of acute myocardial ischemia. Annu Rev Med. 42:225–246. 1991. View Article : Google Scholar : PubMed/NCBI | |
Gottlieb RA, Burleson KO, Kloner RA, Babior BM and Engler RL: Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest. 94:1621–1628. 1994. View Article : Google Scholar : PubMed/NCBI | |
Kajstura J, Cheng W, Reiss K, Clark WA, Sonnenblick EH, Krajewski S, Reed JC, Olivetti G and Anversa P: Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats. Lab Invest. 74:86–107. 1996.PubMed/NCBI | |
Jennings RB, Sommers HM, Smyth GA, Flack HA and Linn H: Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog. Arch Pathol. 70:68–78. 1960.PubMed/NCBI | |
Bertero E, Popoiu TA and Maack C: Mitochondrial calcium in cardiac ischemia/reperfusion injury and cardioprotection. Basic Res Cardiol. 119:569–585. 2024. View Article : Google Scholar : PubMed/NCBI | |
Yang R, Zhang X, Xing P, Zhang S, Zhang F, Wang J, Yu J, Zhu X and Chang P: Grpel2 alleviates myocardial ischemia/reperfusion injury by inhibiting MCU-mediated mitochondrial calcium overload. Biochem Biophys Res Commun. 609:169–175. 2022. View Article : Google Scholar : PubMed/NCBI | |
Guo L, Liu C, Jiang C, Dong Y, Htet Htet Aung L, Ding H and Gao Y: miR-124 inhibits cardiomyocyte apoptosis in myocardial ischaemia-reperfusion injury by activating mitochondrial calcium uniporter regulator 1. Mol Med Rep. 28:1442023. View Article : Google Scholar | |
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 | |
Li C, Ma Q, Toan S, Wang J, Zhou H and Liang J: SERCA overexpression reduces reperfusion-mediated cardiac microvascular damage through inhibition of the calcium/MCU/mPTP/necroptosis signaling pathways. Redox Biol. 36:1016592020. View Article : Google Scholar : PubMed/NCBI | |
Antoniel M, Jones K, Antonucci S, Spolaore B, Fogolari F, Petronilli V, Giorgio V, Carraro M, Di Lisa F, Forte M, et al: The unique histidine in OSCP subunit of F-ATP synthase mediates inhibition of the permeability transition pore by acidic pH. EMBO Rep. 19:257–268. 2018. View Article : Google Scholar | |
Marta K, Hasan P, Rodriguez-Prados M, Paillard M and Hajnoczky G: Pharmacological inhibition of the mitochondrial Ca(2+) uniporter: Relevance for pathophysiology and human therapy. J Mol Cell Cardiol. 151:135–144. 2021. View Article : Google Scholar | |
Rasmussen TP, Wu Y, Joiner ML, Koval OM, Wilson NR, Luczak ED, Wang Q, Chen B, Gao Z, Zhu Z, et al: Inhibition of MCU forces extramitochondrial adaptations governing physiological and pathological stress responses in heart. Proc Natl Acad Sci USA. 112:9129–9134. 2015. View Article : Google Scholar : PubMed/NCBI | |
Chapoy Villanueva H, Sung JH, Stevens JA, Zhang MJ, Nelson PM, Denduluri LS, Feng F, O'Connell TD, Townsend D and Liu JC: Distinct effects of cardiac mitochondrial calcium uniporter inactivation via EMRE deletion in the short and long term. J Mol Cell Cardiol. 181:33–45. 2023. View Article : Google Scholar : PubMed/NCBI | |
Xue Q, Pei H, Liu Q, Zhao M, Sun J, Gao E, Ma X and Tao L: MICU1 protects against myocardial ischemia/reperfusion injury and its control by the importer receptor Tom70. Cell Death Dis. 8:e29232017. View Article : Google Scholar : PubMed/NCBI | |
Simon F, Oberhuber A, Floros N, Busch A, Wagenhäuser MU, Schelzig H and Duran M: Acute Limb Ischemia-Much More Than Just a Lack of Oxygen. Int J Mol Sci. 19:3742018. View Article : Google Scholar : PubMed/NCBI | |
Richards GHC, Hong KL, Henein MY, Hanratty C and Boles U: Coronary artery ectasia: Review of the non-atherosclerotic molecular and pathophysiologic concepts. Int J Mol Sci. 23:51952022. View Article : Google Scholar : PubMed/NCBI | |
Hu Y, Chi L, Kuebler WM and Goldenberg NM: Perivascular Inflammation in Pulmonary Arterial Hypertension. Cells. 9:23382020. View Article : Google Scholar : PubMed/NCBI | |
Cui H, Chen Y, Li K, Zhan R, Zhao M, Xu Y, Lin Z, Fu Y, He Q, Tang PC, et al: Untargeted metabolomics identifies succinate as a biomarker and therapeutic target in aortic aneurysm and dissection. Eur Heart J. 42:4373–4385. 2021. View Article : Google Scholar : PubMed/NCBI | |
Aday AW and Matsushita K: Epidemiology of peripheral artery disease and polyvascular disease. Circ Res. 128:1818–1832. 2021. View Article : Google Scholar : PubMed/NCBI | |
Chan NC, Xu K, de Vries TAC, Eikelboom JW and Hirsh J: Inflammation as a mechanism and therapeutic target in peripheral artery disease. Can J Cardiol. 38:588–600. 2022. View Article : Google Scholar : PubMed/NCBI | |
Archer SL, Weir EK and Wilkins MR: Basic science of pulmonary arterial hypertension for clinicians: New concepts and experimental therapies. Circulation. 121:2045–2066. 2010. View Article : Google Scholar : PubMed/NCBI | |
Dromparis P, Paulin R, Sutendra G, Qi AC, Bonnet S and Michelakis ED: Uncoupling protein 2 deficiency mimics the effects of hypoxia and endoplasmic reticulum stress on mitochondria and triggers pseudohypoxic pulmonary vascular remodeling and pulmonary hypertension. Circ Res. 113:126–136. 2013. View Article : Google Scholar : PubMed/NCBI | |
Hong Z, Chen KH, DasGupta A, Potus F, Dunham-Snary K, Bonnet S, Tian L, Fu J, Breuils-Bonnet S, Provencher S, et al: MicroRNA-138 and MicroRNA-25 Down-regulate mitochondrial calcium uniporter, causing the pulmonary arterial hypertension cancer phenotype. Am J Respir Crit Care Med. 195:515–529. 2017. View Article : Google Scholar : | |
Wu D, Dasgupta A, Read AD, Bentley RET, Motamed M, Chen KH, Al-Qazazi R, Mewburn JD, Dunham-Snary KJ, Alizadeh E, et al: Oxygen sensing, mitochondrial biology and experimental therapeutics for pulmonary hypertension and cancer. Free Radic Biol Med. 170:150–178. 2021. View Article : Google Scholar : PubMed/NCBI | |
Guilluy C, Eddahibi S, Agard C, Guignabert C, Izikki M, Tu L, Savale L, Humbert M, Fadel E, Adnot S, et al: RhoA and Rho kinase activation in human pulmonary hypertension: Role of 5-HT signaling. Am J Respir Crit Care Med. 179:1151–1158. 2009. View Article : Google Scholar : PubMed/NCBI | |
Guo X, Chen KH, Guo Y, Liao H, Tang J and Xiao RP: Mitofusin 2 triggers vascular smooth muscle cell apoptosis via mitochondrial death pathway. Circ Res. 101:1113–1122. 2007. View Article : Google Scholar : PubMed/NCBI | |
Tomida S, Ishima T, Sawaki D, Imai Y, Nagai R and Aizawa K: Multi-Omics of familial thoracic aortic aneurysm and dissection: Calcium transport impairment predisposes aortas to dissection. Int J Mol Sci. 24:152132023. View Article : Google Scholar : PubMed/NCBI | |
Yang H, An BS, Choi KC and Jeung EB: Change of genes in calcium transport channels caused by hypoxic stress in the placenta, duodenum, and kidney of pregnant rats. Biol Reprod. 88:302013. View Article : Google Scholar | |
Garbincius JF and Elrod JW: Mitochondrial calcium exchange in physiology and disease. Physiol Rev. 102:893–992. 2022. View Article : Google Scholar : | |
Wang P, Xu S, Xu J, Xin Y, Lu Y, Zhang H, Zhou B, Xu H, Sheu SS, Tian R and Wang W: Elevated MCU expression by CaMKIIdeltaB limits pathological cardiac remodeling. Circulation. 145:1067–1083. 2022. View Article : Google Scholar : PubMed/NCBI | |
Zhang L, Lu X, Wang J, Li P, Li H, Wei S, Zhou X, Li K, Wang L, Wang R, et al: Zingiberis rhizoma mediated enhancement of the pharmacological effect of aconiti lateralis radix praeparata against acute heart failure and the underlying biological mechanisms. Biomed Pharmacother. 96:246–255. 2017. View Article : Google Scholar : PubMed/NCBI | |
Liu T, Yang N, Sidor A and O'Rourke B: MCU Overexpression rescues inotropy and reverses heart failure by reducing SR Ca(2+) Leak. Circ Res. 128:1191–1204. 2021. View Article : Google Scholar : PubMed/NCBI | |
Garbincius JF and Elrod JW: Is the failing heart starved of mitochondrial calcium? Circ Res. 128:1205–1207. 2021. View Article : Google Scholar : PubMed/NCBI | |
Suarez J, Cividini F, Scott BT, Lehmann K, Diaz-Juarez J, Diemer T, Dai A, Suarez JA, Jain M and Dillmann WH: Restoring mitochondrial calcium uniporter expression in diabetic mouse heart improves mitochondrial calcium handling and cardiac function. J Biol Chem. 293:8182–8195. 2018. View Article : Google Scholar : PubMed/NCBI | |
Tarazón E, Pérez-Carrillo L, García-Bolufer P, Triviño JC, Feijóo-Bandín S, Lago F, González-Juanatey JR, Martínez-Dolz L, Portolés M and Roselló-Lletí E: Circulating mitochondrial genes detect acute cardiac allograft rejection: Role of the mitochondrial calcium uniporter complex. Am J Transplant. 21:2056–2066. 2021. View Article : Google Scholar : | |
Maack C, Cortassa S, Aon MA, Ganesan AN, Liu T and O'Rourke B: Elevated cytosolic Na+ decreases mitochondrial Ca2+ uptake during excitation-contraction coupling and impairs energetic adaptation in cardiac myocytes. Circ Res. 99:172–182. 2006. View Article : Google Scholar : PubMed/NCBI | |
Liu T and O'Rourke B: Enhancing mitochondrial Ca2+ uptake in myocytes from failing hearts restores energy supply and demand matching. Circ Res. 103:279–288. 2008. View Article : Google Scholar : PubMed/NCBI | |
Sommakia S, Houlihan PR, Deane SS, Simcox JA, Torres NS, Jeong MY, Winge DR, Villanueva CJ and Chaudhuri D: Mitochondrial cardiomyopathies feature increased uptake and diminished efflux of mitochondrial calcium. J Mol Cell Cardiol. 113:22–32. 2017. View Article : Google Scholar : PubMed/NCBI | |
Fu DG: Cardiac arrhythmias: Diagnosis, symptoms, and treatments. Cell Biochem Biophys. 73:291–296. 2015. View Article : Google Scholar : PubMed/NCBI | |
Hamilton S, Terentyeva R, Clements RT, Belevych AE and Terentyev D: Sarcoplasmic reticulum-mitochondria communication; implications for cardiac arrhythmia. J Mol Cell Cardiol. 156:105–113. 2021. View Article : Google Scholar : PubMed/NCBI | |
Wang J, Jiang J, Hu H and Chen L: MCU complex: Exploring emerging targets and mechanisms of mitochondrial physiology and pathology. J Adv Res. Feb 27–2024.Epub ahead of print. | |
Langenbacher AD, Shimizu H, Hsu W, Zhao Y, Borges A, Koehler C and Chen JN: Mitochondrial calcium uniporter deficiency in zebrafish causes cardiomyopathy with arrhythmia. Front Physiol. 11:6174922020. View Article : Google Scholar | |
Wiersma M, van Marion DMS, Wüst RCI, Houtkooper RH, Zhang D, Groot NMS, Henning RH and Brundel BJJM: Mitochondrial dysfunction underlies cardiomyocyte remodeling in experimental and clinical atrial fibrillation. Cells. 8:12022019. View Article : Google Scholar : PubMed/NCBI | |
Joseph LC, Reyes MV, Homan EA, Gowen B, Avula UMR, Goulbourne CN, Wan EY, Elrod JW and Morrow JP: The mitochondrial calcium uniporter promotes arrhythmias caused by high-fat diet. Sci Rep. 11:178082021. View Article : Google Scholar : PubMed/NCBI | |
Sripetchwandee J, KenKnight SB, Sanit J, Chattipakorn S and Chattipakorn N: Blockade of mitochondrial calcium uniporter prevents cardiac mitochondrial dysfunction caused by iron overload. Acta Physiol (Oxf). 210:330–341. 2014. View Article : Google Scholar | |
Sander P, Feng M, Schweitzer MK, Wilting F, Gutenthaler SM, Arduino DM, Fischbach S, Dreizehnter L, Moretti A, Gudermann T, et al: Approved drugs ezetimibe and disulfiram enhance mitochondrial Ca(2+) uptake and suppress cardiac arrhythmogenesis. Br J Pharmacol. 178:4518–4532. 2021. View Article : Google Scholar : PubMed/NCBI | |
Hamilton S, Terentyeva R, Perger F, Hernández Orengo B, Martin B, Gorr MW, Belevych AE, Clements RT, Györke S and Terentyev D: MCU overexpression evokes disparate dose-dependent effects on mito-ROS and spontaneous Ca(2+) release in hypertrophic rat cardiomyocytes. Am J Physiol Heart Circ Physiol. 321:H615–H632. 2021. View Article : Google Scholar : PubMed/NCBI | |
Hu X, Wang H, Lu W, Dong Y and Cheng P: The study on intramyocardial calcium overload and apoptosis induced by coxsackievirus B3. J Tongji Med Univ. 21:256–258. 2622001. | |
Salgado DM, Eltit JM, Mansfield K, Panqueba C, Castro D, Vega MR, Xhaja K, Schmidt D, Martin KJ, Allen PD, et al: Heart and skeletal muscle are targets of dengue virus infection. Pediatr Infect Dis J. 29:238–242. 2010. View Article : Google Scholar : | |
Huynh TV, Rethi L, Lee TW, Higa S, Kao YH and Chen YJ: Spike protein impairs mitochondrial function in human cardiomyocytes: Mechanisms underlying cardiac injury in COVID-19. Cells. 12:8772023. View Article : Google Scholar : PubMed/NCBI | |
Maass DL, White J, Sanders B and Horton JW: Role of cytosolic vs. mitochondrial Ca2+ accumulation in burn injury-related myocardial inflammation and function. Am J Physiol Heart Circ Physiol. 288:H744–H751. 2005. View Article : Google Scholar | |
Wan-Yi L, Hui, Zong-Cheng Y and Yue-Sheng H: Ruthenium red attenuated cardiomyocyte and mitochondrial damage during the early stage after severe burn. Burns. 28:35–38. 2002. View Article : Google Scholar : PubMed/NCBI | |
White DJ, Maass DL, Sanders B and Horton JW: Cardiomyocyte intracellular calcium and cardiac dysfunction after burn trauma. Crit Care Med. 30:14–22. 2002. View Article : Google Scholar : PubMed/NCBI | |
Lim CC, Zuppinger C, Guo X, Kuster GM, Helmes M, Eppenberger HM, Suter TM, Liao R and Sawyer DB: Anthracyclines induce calpain-dependent titin proteolysis and necrosis in cardiomyocytes. J Biol Chem. 279:8290–8299. 2004. View Article : Google Scholar | |
Gunter TE and Pfeiffer DR: Mechanisms by which mitochondria transport calcium. Am J Physiol. 258:C755–C786. 1990. View Article : Google Scholar : PubMed/NCBI | |
Gunter TE, Gunter KK, Sheu SS and Gavin CE: Mitochondrial calcium transport: Physiological and pathological relevance. Am J Physiol. 267:C313–C339. 1994. View Article : Google Scholar : PubMed/NCBI | |
Garbincius JF, Luongo TS and Elrod JW: The debate continues - What is the role of MCU and mitochondrial calcium uptake in the heart? J Mol Cell Cardiol. 143:163–174. 2020. View Article : Google Scholar : PubMed/NCBI | |
Ashok D, Papanicolaou K, Sidor A, Wang M, Solhjoo S, Liu T and O'Rourke B: Mitochondrial membrane potential instability on reperfusion after ischemia does not depend on mitochondrial Ca(2+) uptake. J Biol Chem. 299:1047082023. View Article : Google Scholar : PubMed/NCBI | |
Wang C, Jacewicz A, Delgado BD, Baradaran R and Long SB: Structures reveal gatekeeping of the mitochondrial Ca(2+) uniporter by MICU1-MICU2. Elife. 9:e599912020. View Article : Google Scholar : PubMed/NCBI | |
Xie A, Song Z, Liu H, Zhou A, Shi G, Wang Q, Gu L, Liu M, Xie LH, Qu Z and Dudley SC Jr: Mitochondrial Ca(2+) influx contributes to arrhythmic risk in nonischemic cardiomyopathy. J Am Heart Assoc. 7:e0078052018. View Article : Google Scholar : PubMed/NCBI | |
Tomar D, Jaña F, Dong Z, Quinn WJ III, Jadiya P, Breves SL, Daw CC, Srikantan S, Shanmughapriya S, Nemani N, et al: Blockade of MCU-mediated Ca(2+) uptake perturbs lipid metabolism via PP4-dependent AMPK dephosphorylation. Cell Rep. 26:3709–3725 e7. 2019. View Article : Google Scholar : PubMed/NCBI | |
Tian S, Lei P, Zhang J, Sun Y, Li B and Shan Y: Sulforaphane Balances Ca(2+) homeostasis injured by excessive fat via mitochondria-associated membrane (MAM). Mol Nutr Food Res. 65:e20010762021. View Article : Google Scholar : PubMed/NCBI | |
Wright LE, Vecellio Reane D, Milan G, Terrin A, Di Bello G, Belligoli A, Sanna M, Foletto M, Favaretto F, Raffaello A, et al: Increased mitochondrial calcium uniporter in adipocytes underlies mitochondrial alterations associated with insulin resistance. Am J Physiol Endocrinol Metab. 313:E641–E650. 2017. View Article : Google Scholar : PubMed/NCBI | |
Zhang Z, Luo Z, Yu L, Xiao Y, Liu S, Aluo Z, Ma Z, Huang L, Xiao L, Jia M, et al: Ruthenium 360 and mitoxantrone inhibit mitochondrial calcium uniporter channel to prevent liver steatosis induced by high-fat diet. Br J Pharmacol. 179:2678–2696. 2022. View Article : Google Scholar | |
Jia M, Liu S, Xiao Y, Zhang Z, Li M, Qi X, Qi X, Yu L, Zhang C, Jiang T, et al: Deletion of the mitochondrial calcium uniporter in adipose tissue promotes energy expenditure and alleviates diet-induced obesity. Mol Metab. 80:1018732024. View Article : Google Scholar : PubMed/NCBI | |
Arruda AP and Hotamisligil GS: Calcium Homeostasis and organelle function in the pathogenesis of obesity and diabetes. Cell Metab. 22:381–397. 2015. View Article : Google Scholar : PubMed/NCBI | |
Kannel WB, Wolf PA, Benjamin EJ and Levy D: Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol. 82:2N–9N. 1998. View Article : Google Scholar : PubMed/NCBI | |
Grisanti LA: Diabetes and Arrhythmias: Pathophysiology, mechanisms and therapeutic outcomes. Front Physiol. 9:16692018. View Article : Google Scholar : PubMed/NCBI | |
Cividini F, Scott BT, Suarez J, Casteel DE, Heinz S, Dai A, Diemer T, Suarez JA, Benner CW, Ghassemian M and Dillmann WH: Ncor2/PPARalpha-dependent upregulation of MCUb in the type 2 diabetic heart impacts cardiac metabolic flexibility and function. Diabetes. 70:665–679. 2021. View Article : Google Scholar | |
Shi X, Liu C, Chen J, Zhou S, Li Y, Zhao X, Xing J, Xue J, Liu F and Li F: Endothelial MICU1 alleviates diabetic cardiomyopathy by attenuating nitrative stress-mediated cardiac microvascular injury. Cardiovasc Diabetol. 22:2162023. View Article : Google Scholar : PubMed/NCBI | |
Ji L, Liu F, Jing Z, Huang Q, Zhao Y, Cao H, Li J, Yin C, Xing J and Li F: MICU1 alleviates diabetic cardiomyopathy through mitochondrial Ca(2+)-dependent antioxidant response. Diabetes. 66:1586–1600. 2017. View Article : Google Scholar : PubMed/NCBI | |
De Stefani D, Rizzuto R and Pozzan T: Enjoy the trip: Calcium in mitochondria back and forth. Annu Rev Biochem. 85:161–192. 2016. View Article : Google Scholar : PubMed/NCBI | |
Kon N, Murakoshi M, Isobe A, Kagechika K, Miyoshi N and Nagayama T: DS16570511 is a small-molecule inhibitor of the mitochondrial calcium uniporter. Cell Death Discov. 3:170452017. View Article : Google Scholar : PubMed/NCBI | |
Arduino DM, Wettmarshausen J, Vais H, Navas-Navarro P, Cheng Y, Leimpek A, Ma Z, Delrio-Lorenzo A, Giordano A, Garcia-Perez C, et al: Systematic identification of MCU modulators by orthogonal interspecies chemical screening. Mol Cell. 67:711–723 e7. 2017. View Article : Google Scholar : PubMed/NCBI | |
Paillard M, Csordás G, Huang KT, Várnai P, Joseph SK and Hajnóczky G: MICU1 interacts with the D-ring of the MCU pore to control its Ca(2+) flux and sensitivity to Ru360. Mol Cell. 72:778–785 e3. 2018. View Article : Google Scholar : PubMed/NCBI | |
Xu X, Zhou B, Liu J, Ma Q, Zhang T and Wu X: Ru360 alleviates postoperative cognitive dysfunction in aged mice by inhibiting MCU-mediated mitochondrial dysfunction. Neuropsychiatr Dis Treat. 19:1531–1542. 2023. View Article : Google Scholar : PubMed/NCBI | |
Bigham NP, Novorolsky RJ, Davis KR, Zou H, MacMillan SN, Stevenson MJ, Robertson GS and Wilson JJ: Supramolecular delivery of dinuclear ruthenium and osmium MCU inhibitors. Inorg Chem Front. 11:5064–5079. 2024. View Article : Google Scholar : PubMed/NCBI | |
Thu VT, Kim HK, Long le T, Lee SR, Hanh TM, Ko TH, Heo HJ, Kim N, Kim SH, Ko KS, et al: NecroX-5 prevents hypoxia/reoxygenation injury by inhibiting the mitochondrial calcium uniporter. Cardiovasc Res. 94:342–350. 2012. View Article : Google Scholar : PubMed/NCBI | |
Schwartz J, Holmuhamedov E, Zhang X, Lovelace GL, Smith CD and Lemasters JJ: Minocycline and doxycycline, but not other tetracycline-derived compounds, protect liver cells from chemical hypoxia and ischemia/reperfusion injury by inhibition of the mitochondrial calcium uniporter. Toxicol Appl Pharmacol. 273:172–179. 2013. View Article : Google Scholar : PubMed/NCBI | |
Xiao Z, Guan L, Shi H, Yu Y, Yu Z, Qin S, Su Y, Chen R, Li M and Ge J: Trimetazidine affects mitochondrial calcium uniporter expression to restore ischemic heart function via reactive oxygen species/NFĸB pathway inhibition. J Cardiovasc Pharmacol. 82:104–116. 2023. View Article : Google Scholar : PubMed/NCBI | |
Chaudhary P, Sharma YK, Sharma S, Singh SN and Suryakumar G: High altitude mediated skeletal muscle atrophy: Protective role of curcumin. Biochimie. 156:138–147. 2019. View Article : Google Scholar | |
Kotha RR and Luthria DL: Curcumin: Biological, pharmaceutical, nutraceutical, and analytical aspects. Molecules. 24:29302019. View Article : Google Scholar : PubMed/NCBI | |
Kushwaha AD, Kalra N, Varshney R and Saraswat D: Mitochondrial Ca(2+) overload due to altered proteostasis amplifies apoptosis in C2C12 myoblasts under hypoxia: Protective role of nanocurcumin formulation. IUBMB Life. 75:673–687. 2023. View Article : Google Scholar : PubMed/NCBI | |
Dong Z, Zhang C, Chen Y, Chen Y, Yuan Z, Peng Y and Cao T: Astragaloside-IV protects against heat-induced apoptosis by inhibiting excessive activation of mitochondrial Ca2+ uniporter. Cell Physiol Biochem. 42:480–494. 2017. View Article : Google Scholar : PubMed/NCBI | |
Jiang C, Shen J, Wang C, Huang Y, Wang L, Yang Y, Hu W, Li P and Wu H: Mechanism of aconitine mediated neuronal apoptosis induced by mitochondrial calcium overload caused by MCU. Toxicol Lett. 384:86–95. 2023. View Article : Google Scholar : PubMed/NCBI | |
Gao Y, Hou R, Fei Q, Fang L, Han Y, Cai R, Peng C and Qi Y: The three-herb formula shuang-huang-lian stabilizes mast cells through activation of mitochondrial calcium uniporter. Sci Rep. 7:387362017. View Article : Google Scholar : PubMed/NCBI | |
Ding J, Ji R, Wang Z, Jia Y, Meng T, Song X, Gao J and He Q: Cardiovascular protection of YiyiFuzi powder and the potential mechanisms through modulating mitochondria-endoplasmic reticulum interactions. Front Pharmacol. 15:14055452024. View Article : Google Scholar : PubMed/NCBI | |
Cao J, Zheng CD, Zhang GH, Zhang YJ and Min S: Protective effect of Shenfu injection on myocardial mitochondria injured by ischemia-reperfusion in rabbits. Chin Med J (Engl). 118:505–507. 2005.PubMed/NCBI | |
Wen J, Zhang L, Liu H, Wang J, Li J, Yang Y, Wang Y, Cai H, Li R and Zhao Y: Salsolinol attenuates doxorubicin-induced chronic heart failure in rats and improves mitochondrial function in H9c2 cardiomyocytes. Front Pharmacol. 10:11352019. View Article : Google Scholar : PubMed/NCBI | |
Meng M, Jiang Y, Wang Y, Huo R, Ma N, Shen X and Chang G: β-carotene targets IP3R/GRP75/VDAC1-MCU axis to renovate LPS-induced mitochondrial oxidative damage by regulating STIM1. Free Radic Biol Med. 205:25–46. 2023. View Article : Google Scholar : PubMed/NCBI | |
Luo D, Zhao Y, Fang Z, Zhao Y, Han Y, Piao J, Rong X and Guo J: Tianhuang formula regulates adipocyte mitochondrial function by AMPK/MICU1 pathway in HFD/STZ-induced T2DM mice. BMC Complement Med Ther. 23:2022023. View Article : Google Scholar : PubMed/NCBI | |
Wang P, Zheng X, Du R, Xu J, Li J, Zhang H, Liang X and Liang H: Astaxanthin protects against alcoholic liver injury via regulating mitochondrial redox balance and calcium homeostasis. J Agric Food Chem. 71:19531–19550. 2023. View Article : Google Scholar : PubMed/NCBI | |
Lei Y, Yang HY, Meng N, Qin YY, Xu MT, Xiang XL, Liu L and Tang GD: Mitochondrial calcium uniporter promotes mitophagy by regulating the PINK1/Parkin pathway in caerulein-treated pancreatic ductal epithelial cells in vitro. Exp Ther Med. 27:1472024. View Article : Google Scholar | |
Hou Y, Fan F, Xie N, Zhang Y, Wang X and Meng X: Rhodiola crenulata alleviates hypobaric hypoxia-induced brain injury by maintaining BBB integrity and balancing energy metabolism dysfunction. Phytomedicine. 128:1555292024. View Article : Google Scholar : PubMed/NCBI | |
Liu H, Li Q, Zhang X, Shi Y and Li J: Effect of ginkgolide K on calcium channel activity in Alzheimer's disease. Exp Ther Med. 23:4262022. View Article : Google Scholar : PubMed/NCBI |