Mitophagy is a selective autophagic process that identifies and eliminates dysfunctional mitochondria during cellular stress. Its primary function is to limit the excessive production of ROS and the release of pro-apoptotic signals from damaged mitochondria. Thus, mitophagy prevents the amplification of mitochondrial injury and reduces cellular toxicity (18). Simultaneously, the degradation products generated through mitophagy can be reutilized to support cellular energy metabolism and biosynthesis, rendering mitophagy the first line of defense in the MQC system (19).

Mitophagy is primarily mediated via two complementary pathways: Ubiquitin-dependent and receptor-mediated ubiquitin-independent mechanisms (20). The ubiquitin-dependent pathway is characterized by activation of the PTEN-induced kinase 1 (PINK1)-Parkin axis, and is primarily triggered by mitochondrial depolarization and related damage signals (21,22). By contrast, receptor-mediated mitophagy relies on outer mitochondrial membrane receptors, including BCL2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3), BCL2/adenovirus E1B 19-kDa-interacting protein 3-like (BNIP3L; also known as NIX) and FUN14 domain containing 1 (FUNDC1), which directly interact with LC3 and serve prominent roles under hypoxic and oxidative stress conditions (23,24). These pathways function in a complementary manner depending on the nature and intensity of cellular stress (25).

From a regulatory perspective, mitophagy exhibits pronounced temporal dependence, selectivity and a context-dependent effect. During the early phase of mitochondrial injury, mitophagy is rapidly activated to selectively eliminate severely damaged mitochondria (26). As injury resolves, mitophagy activity gradually declines and becomes coordinated with subsequent mitochondrial biogenesis, forming a continuous ‘clearance-regeneration’ regulatory sequence (27). Appropriately regulated mitophagy promotes hepatocyte survival and tissue repair, whereas excessive or prolonged activation may result in aberrant degradation of functional mitochondria, leading to metabolic imbalance and exacerbation of liver injury (28).

Notably, mitophagy should not be interpreted as uniformly protective in ALI. The net effect of mitophagy depends on injury severity, timing and the capacity of mitochondrial biogenesis to replenish mitochondrial content. Insufficient mitophagy permits the accumulation of damaged mitochondria and amplifies ROS production (13), whereas excessive or prolonged mitophagy may deplete functional mitochondria and aggravate energy failure (29). Therefore, the therapeutic goal should be to restore balanced mitochondrial turnover rather than indiscriminately activate mitophagy.

Mitochondrial biogenesis refers to the generation of new mitochondria through the coordinated regulation of nuclear genes and the mitochondrial genome [mitochondrial DNA (mtDNA)], followed by the integration of newly formed mitochondria into the existing network. As the regenerative arm of MQC, mitochondrial biogenesis serves a critical role in replenishing mitochondrial mass, restoring oxidative phosphorylation capacity, and supporting hepatocyte repair and regeneration (30).

Mitochondrial biogenesis is gradually activated during the intermediate to late stages of ALI, and its activation strength is closely associated with tissue repair capacity (31). The central regulatory axis of mitochondrial biogenesis is organized around peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α). PGC-1α cooperates with transcriptional regulators, such as nuclear factor erythroid 2-related factor (NRF)1/2 and mitochondrial transcription factor A (TFAM) to promote the expression of nuclear-encoded mitochondrial proteins, mtDNA replication and mtDNA transcription (32,33). Energy-sensing pathways, including the AMP-activated protein kinase (AMPK)-sirtuin 1 (SIRT1) pathway, modulate PGC-1α activity, thereby tightly coupling cellular metabolic status to mitochondrial regenerative responses (34).

Mitochondrial biogenesis is characterized by clear temporal and stress dependence (35). Its activation typically lags behind mitophagy and proceeds in parallel with hepatocellular recovery (36). Moreover, mitochondrial biogenesis is closely coordinated with mitophagy and mitochondrial dynamics. Autophagic degradation products, including amino acids, fatty acids and nucleotides, serve as substrates for macromolecular biosynthesis, whereas dynamic remodeling of the mitochondrial network provides a structural framework that promotes the incorporation of newly generated mitochondria (37).

A major unresolved issue is whether mitochondrial biogenesis drives hepatocellular recovery or is merely a secondary marker of tissue repair. Most current evidence is derived from changes in PGC-1α, NRF1/2 or TFAM expression, whereas direct functional validation of newly generated mitochondria remains limited (38,39). Future studies should combine molecular marker detection with analyses of mitochondrial respiratory function, including oxygen consumption and oxidative phosphorylation capacity, mtDNA replication and longitudinal assessment of mitochondrial recovery.

Mitochondrial dynamics describe the continuous regulation of mitochondrial morphology and network architecture through the balance between fission and fusion, and represent the structural remodeling component of MQC (40). Their core function is to segregate locally damaged mitochondria through fission, thereby generating substrates for subsequent mitophagy, whereas fusion enables complementation of mitochondrial contents to preserve network integrity and metabolic efficiency (41).

Mitochondrial fission is primarily mediated by dynamin-related protein 1 (DRP1), whereas fusion is coordinated by mitofusin (MFN)1/2 and optic atrophy 1 (42). Under conditions of mitochondrial damage and oxidative stress, the dynamic balance generally shifts toward fission, facilitating the isolation and clearance of dysfunctional mitochondria (17). During the recovery phase, fusion activity progressively increases, supporting the reconstruction of the mitochondrial network and functional compensation. Dysregulation of mitochondrial dynamics may lead to excessive fragmentation or abnormal elongation, thereby amplifying oxidative stress and metabolic dysfunction, and accelerating hepatocellular injury (43).

Although excessive mitochondrial fission is commonly associated with the progression of injury, mitochondrial fragmentation may also represent an adaptive step that segregates damaged mitochondrial segments for mitophagy. Thus, the complete inhibition of fission may be detrimental in certain contexts. The key issue is not whether fission or fusion is beneficial but whether mitochondrial dynamics are appropriately synchronized with mitophagy and biogenesis.

Mitophagy, mitochondrial biogenesis and mitochondrial dynamics form a highly interconnected regulatory network. These modules collectively maintain mitochondrial homeostasis through temporal coordination, functional complementarity and signal integration (44). At a systems level, these modules follow a common regulatory sequence of ‘clearance first, remodeling next and regeneration last’ (45,46). In the early phase of ALI, mitochondrial dynamics shift toward fission and cooperate with mitophagy to eliminate damaged mitochondria (47). Subsequently, these dynamics progressively favor fusion to remodel the mitochondrial network. During the intermediate to late phases, mitochondrial biogenesis is activated, enabling the generation and integration of new mitochondria and promoting functional recovery (48).

At the signaling level, multiple pathways participate in coordinating these three MQC modules. Among them, AMPK-SIRT1 functions as a central energy-sensing hub that integrates mitophagy activation, dynamic balance adjustment and the initiation of mitochondrial biogenesis (49). NRF2 indirectly modulates mitochondrial dynamics and promotes regenerative responses by alleviating oxidative stress (50). Mitochondrial-nuclear communication may also contribute to the adjustment of MQC activation strength and timing according to the extent of mitochondrial damage (14,51).

Although MQC operates within a unified regulatory framework, its activation patterns exhibit substantial heterogeneity across different ALI etiologies and among distinct hepatocyte subpopulations (52). This heterogeneity directly influences mitochondrial repair efficiency and cell fate decisions, and provides a theoretical basis for subsequent etiology-oriented precision intervention strategies.

DILI is one of the most common causes of ALI, with acetaminophen (APAP) overdose and injury associated with herbal medicines or dietary supplements being the most common (54). Mitochondrial damage in DILI is direct and dose-dependent. It mainly results from reactive drug metabolites, such as N-acetyl-p-benzoquinone imine, generated during APAP metabolism, which directly interacts with mitochondrial proteins (55,56). These interactions lead to the collapse of mitochondrial membrane potential, excessive ROS production and mtDNA damage. Under these conditions, MQC activation in DILI is characterized by a pronounced context-dependent role of mitophagy, with NRF2 signaling acting as the dominant upstream regulator (57). Reduced NRF2 activity markedly impairs PINK1 expression and delays mitophagy activation in APAP-induced liver injury models, thus resulting in excessive accumulation of damaged mitochondria and the expansion of hepatocellular necrosis (58,59). By contrast, enhanced NRF2 activation promotes mitophagy and mitochondrial biogenesis, thereby improving hepatocyte survival and alleviating tissue injury (60).

MQC activation in DILI generally follows a sequential pattern consisting of early mitophagy activation, intermediate remodeling of mitochondrial dynamics and late induction of mitochondrial biogenesis (46,52). During the early phase after injury, rapid ROS accumulation activates the PINK1-Parkin pathway and NRF2 signaling, inducing mitophagy to eliminate severely damaged mitochondria (61). In the intermediate phase, mitochondrial dynamics shift toward enhanced fission accompanied by suppressed fusion, facilitating further segregation and clearance of dysfunctional mitochondria (47). At later stages, NRF2-driven upregulation of PGC-1α initiates mitochondrial biogenesis, replenishing mitochondrial content and gradually restoring oxidative phosphorylation capacity (33). Mitophagy exhibits the most prominent dual effect in DILI; moderate activation under low-dose exposure is protective, whereas excessive activation under high-dose conditions may result in aberrant degradation of functional mitochondria, leading to energy collapse and aggravated liver injury (62).

IRI commonly occurs during liver surgery, transplantation or hemorrhagic shock. Pathophysiologically, it involves energy deprivation during ischemia, followed by an abrupt oxidative burst upon reperfusion (63). Unlike in DILI, mitochondrial damage in IRI is characterized by the coexistence of energy-sensing dysregulation and structural disruption. Accordingly, MQC regulation in IRI is functionally dominated by the AMPK-SIRT1 axis and features a tight coupling between mitochondrial fission and mitophagy (64). Experimental evidence indicates impaired mitophagy, including inhibition of DRP1-Beclin-1-dependent mitophagy, compromises the clearance of damaged mitochondria and exacerbates ROS-mediated hepatocellular injury in ischemia-reperfusion models (65,66). By contrast, activation of the AMPK-SIRT1 pathway accelerates the initiation of mitochondrial biogenesis and facilitates the recovery of cellular ATP levels (67).

MQC activation in IRI follows a continuous sequence consisting of ischemia-associated remodeling of mitochondrial dynamics, reperfusion-driven mitophagy and recovery-phase mitochondrial biogenesis (64). During the ischemic phase, rapid ATP depletion increases the AMP/ATP ratio and activates AMPK, which phosphorylates DRP1 to promote mitochondrial fission and preemptively segregate vulnerable mitochondria (65). In the early reperfusion phase, massive oxygen influx induces a burst of ROS, and AMPK further activates receptor-mediated mitophagy pathways involving BNIP3, enabling the rapid removal of severely damaged mitochondria (64,65). During the subsequent recovery phase, sustained activation of the AMPK-SIRT1 axis promotes PGC-1α-dependent mitochondrial biogenesis, gradually restoring hepatocellular energy homeostasis (49). Collectively, BNIP3-mediated mitophagy and DRP1-dependent mitochondrial fission constitute the key rate-limiting steps in MQC regulation during IRI, and their coordinated efficiency largely determines injury severity and repair capacity.

Viral ALI results from hepatotropic viral infections, such as hepatitis A virus and hepatitis E virus, and is characterized by a dual origin of mitochondrial damage: Direct viral interference with mitochondrial structure and function, and secondary amplification driven by immune-mediated inflammation and oxidative stress (68). In this context, MQC regulation is characterized by extensive crosstalk between innate immune signaling and MQC, along with persistent suppression of mitochondrial biogenesis (69).

During viral infection, hepatotropic viruses such as hepatitis A and E viruses consume substantial mitochondrial energy to support viral replication, and viral proteins directly compromise mitochondrial membrane integrity (69,70). Simultaneously, cytokines released by natural killer cells and cytotoxic T lymphocytes promote excessive ROS production, further aggravating mitochondrial injury (71–73). Consequently, MQC activation follows a characteristic pattern consisting of early mitophagy activation, intermediate disruption of mitochondrial dynamics and late-stage impairment of mitochondrial biogenesis (74). In the early phase of infection, virus-induced oxidative stress activates the PINK1-Parkin pathway, thereby promoting mitophagy to eliminate damaged mitochondria (75,76). During the intermediate phase, viral proteins suppress MFN1/2 expression, resulting in impaired mitochondrial fusion and fragmentation of the mitochondrial network (74,77). In the later phase, viral interference with PGC-1α signaling inhibits mitochondrial biogenesis, thereby constraining the hepatocellular repair capacity (78).

At the molecular level, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-PINK1 axis represents a critical intersection between MQC regulation and the innate immune response in viral ALI. mtDNA released from damaged mitochondria activates cGAS-STING signaling, which amplifies inflammatory responses and enhances PINK1 expression and mitophagy activation (79,80). In contrast to DILI and IRI, the sustained suppression of mitochondrial biogenesis is a defining feature of viral ALI. Viral downregulation of TFAM directly impairs mtDNA transcription and replication, restricting the generation of new mitochondria and preventing completion of the MQC ‘clearance-regeneration’ repair cycle (81). These findings suggest that the disruption of mitochondrial biogenesis and TFAM-related mtDNA maintenance impairs mitochondrial recovery during viral infection. However, whether the direct restoration of TFAM improves hepatocyte survival in viral ALI remains unclear (81,82).

Taken together, the aforementioned evidence highlights MQC as a highly adaptive and etiology-dependent regulatory network in ALI. Although mitophagy, mitochondrial biogenesis and mitochondrial dynamics operate within a shared conceptual framework, their relative activation timings, dominant regulatory pathways and degrees of coordination vary substantially across different forms of ALI. In DILI, MQC regulation is largely driven by NRF2 signaling and is characterized by a prominent dual role of mitophagy: Appropriate activation enables completion of the clearance-regeneration cycle, whereas excessive activation exacerbates metabolic collapse (83). In IRI, MQC is predominantly governed by energy-sensing mechanisms centered on the AMPK-SIRT1 axis, with tight coupling between mitochondrial fission and mitophagy, enabling the efficient removal of damaged mitochondria and subsequent bioenergetic recovery (65). By contrast, viral ALI can be distinguished by sustained interference with mitochondrial biogenesis. This pattern is driven by the persistent innate immune activation and viral suppression of mitochondrial transcriptional programs. Consequently, the MQC repair loop remains incomplete despite early induction of mitophagy (81).

These etiology-specific MQC patterns indicate that mitochondrial responses in ALI are not uniform stress reactions but dynamically tuned processes shaped by the nature, intensity and duration of the injurious stimulus. The efficiency of hepatocellular recovery depends not only on the activation of individual MQC modules but also on their coordinated integration into a functional repair sequence. Disruption of this coordination, such as excessive mitophagy without compensatory biogenesis, can shift MQC from a protective to a maladaptive response (14,35). Recognizing MQC as a context-dependent and temporally staged regulatory network provides a mechanistic basis for stratified therapeutic intervention and sets the stage for the targeted modulation of MQC pathways in ALI.

Several issues in this field remain unresolved. First, the protective vs. maladaptive role of mitophagy remains context-dependent, and the threshold at which mitophagy shifts from mitochondrial repair to depletion remains unclear. Second, mitochondrial fission may facilitate the segregation of damaged mitochondria or promote excessive fragmentation, depending on the timing and severity of injury. Third, increased expression of mitochondrial biogenesis markers does not necessarily indicate functional recovery of mitochondrial respiration. Finally, the findings from APAP-induced ALI, IRI and viral ALI models may not be directly interchangeable. These uncertainties highlight the need for temporally resolved and etiology-specific studies on MQC in ALI. The major etiology-specific MQC patterns in different forms of ALI are summarized in Table I.

Small-molecule drugs represent the most extensively investigated class of MQC-targeted interventions in ALI because of their defined molecular targets and translational feasibility (85). A major therapeutic strategy involves enhancing autophagy and mitophagy by modulating the energy-sensing AMPK-mammalian target of rapamycin (mTOR) axis (86). AMPK activation, for example, by metformin, promotes autophagic clearance of damaged mitochondria, whereas inhibition of mTOR signaling by agents such as rapamycin facilitates mitophagy and has demonstrated hepatoprotective effects in experimental models of DILI (87,88). By reinforcing endogenous mitochondrial turnover mechanisms, these agents limit the accumulation of dysfunctional ROS-generating mitochondria and attenuate downstream inflammatory signaling (62). Activation of PINK1-Parkin-mediated mitophagy not only removes compromised mitochondria but also suppresses inflammasome activation in stressed hepatocytes (89).

Beyond mitophagy induction, pharmacological modulation of mitochondrial dynamics has emerged as an important option for MQC-targeted therapy (90). Excessive mitochondrial fission, largely mediated by DRP1, contributes to mitochondrial fragmentation and metabolic failure in ALI (91). Accordingly, DRP1 inhibition by Mdivi-1 has been reported to alleviate cecal ligation and puncture-induced sepsis-associated liver injury, at least in part, by suppressing STING signaling activation in Kupffer cells and attenuating systemic inflammatory responses (92). Conversely, strategies that enhance mitochondrial fusion or stimulate mitochondrial biogenesis can improve cellular bioenergetic capacity. Small molecules that activate SIRT1/PGC-1α-related signaling restore mitochondrial function and promote mitochondrial biogenesis in experimental hepatic IRI (67).

Beyond these canonical pathways, small-molecule modulators of the BCL-2 family of proteins are also being explored for their ability to indirectly trigger mitophagy (93). The inhibition of the anti-apoptotic protein MCL-1 by compounds such as UMI-77 has been reported to induce mitophagy in non-hepatic preclinical models. Although these findings suggest that pharmacological induction of mitophagy is therapeutically relevant, its role in ALI remains unclear (94,95). Collectively, these pharmacological approaches act on distinct but interconnected nodes of the MQC network, including mitophagy induction, dynamic remodeling and mitochondrial regeneration, and converge to preserve mitochondrial homeostasis and reduce hepatocyte death in ALI.

Naturally derived compounds have attracted increasing attention as modulators of MQC in ALI, largely owing to their pleiotropic biological activities and favorable safety profiles. Several of these compounds exert hepatoprotective effects by simultaneously targeting oxidative stress, mitochondrial turnover and bioenergetic homeostasis, thereby influencing multiple nodes of the MQC network (96).

Plant-derived polyphenols and antioxidants have been the most extensively studied group in this category. Resveratrol, a prototypical polyphenol, has been reported to alleviate experimental liver injury by reducing oxidative stress and inflammatory responses, and inducing SIRT1/p62-mediated mitophagy (97). These findings suggest that resveratrol preserves mitochondrial homeostasis mainly through SIRT1-related mitophagy and redox regulation, although most evidence remains preclinical and model-dependent (97). Similarly, quercetin has been reported to improve acute liver failure by modulating mitophagy-related apoptosis and inflammatory responses through the PPARγ/PGC-1α/NF-κB axis (98). Curcumin has also shown hepatoprotective potential, primarily through antioxidant and anti-inflammatory mechanisms, including the activation of NRF2 signaling and inhibition of NF-κB activation; however, direct evidence linking curcumin to hepatic mitophagy in ALI remains limited (99). By limiting ROS accumulation and facilitating the removal of dysfunctional mitochondria, these compounds help maintain the mitochondrial membrane potential and ATP production in stressed hepatocytes (61).

In addition to phytochemicals, several endogenous molecules and nutritional supplements have been implicated in MQC regulation (100). Melatonin has been reported to attenuate experimental liver IRI by modulating mitochondrial injury-related pathways, supporting its potential role in mitochondrial protection during ALI (101). Coenzyme Q10, a mitochondrial electron carrier and lipid-soluble antioxidant, may theoretically support mitochondrial redox homeostasis and bioenergetic functions, although ALI-specific evidence remains limited (102). Moreover, several natural compounds have been reported to regulate PGC-1α-related mitochondrial biogenesis in non-ALI metabolic models. These findings suggest a link between natural compounds and mitochondrial regeneration; however, their relevance to ALI requires further validation (103,104).

Collectively, natural compounds modulate MQC through their integrated effects on redox homeostasis, mitophagy activation and mitochondrial regeneration. Although most evidence remains at the preclinical level, the multitarget actions of these agents make them attractive complementary candidates for MQC-based intervention strategies for ALI.

Beyond conventional pharmacological approaches, gene- and cell-based therapies represent innovative strategies for targeting MQC in ALI. Emerging bioengineering technologies have further expanded this therapeutic landscape by enabling direct restoration of mitochondrial homeostasis (105).

Gene-based strategies focus on precise manipulation of key regulators that govern mitophagy, mitochondrial biogenesis and responses to oxidative stress. Targeted delivery or overexpression of genes such as PINK1, Parkin, PGC-1α and NRF2 has been shown to enhance mitochondrial clearance, regeneration and antioxidant capacity in preclinical models of ALI (52,83). Conversely, genetic inhibition of maladaptive pathways, including excessive mitochondrial fission and mtDNA-driven inflammatory signaling, can mitigate hepatocellular damage while preserving essential MQC functions. Although still largely experimental, these approaches highlight the potential for directly reprogramming mitochondrial stress responses at the molecular level.

Cell-based therapies provide an additional dimension of MQC modulation by exploiting the regenerative and immunomodulatory properties of stem cells. In particular, mesenchymal stem cells (MSCs) enhance mitochondrial function through paracrine signaling, attenuation of oxidative stress and suppression of inflammation (106). Accumulating evidence has indicated that MSCs and their extracellular vesicles facilitate the transfer of functional mitochondria or mitochondrial components to injured cells, thereby restoring their bioenergetic capacity and enhancing cellular resilience (106,107). This mitochondria-centered repair mechanism represents a unique advantage of cell-based approaches in severe mitochondrial dysfunction.

Emerging bioengineering technologies have expanded the therapeutic landscape by enabling targeted and efficient modulation of MQC at the subcellular level (108). Advances in mitochondrial transplantation, mitochondria-targeted drug delivery systems and nanotechnology-based platforms, such as the transplantation of isolated healthy mitochondria and the use of mitochondria-targeted nanocarriers to deliver antioxidants or other therapeutic agents (109,110), have enabled the selective enhancement of mitochondrial function, suppression of oxidative stress at its source and promotion of network recovery with high spatial precision. Although these technologies remain in the early stages of development, they offer promising solutions to the longstanding challenges related to targeting specificity and therapeutic efficacy.

Collectively, gene- and cell-based interventions and emerging technologies reflect a paradigm shift from indirect modulation to direct restoration of mitochondrial integrity. By reinforcing MQC at the genetic, cellular and subcellular levels, these approaches have a substantial potential to complement existing therapies and enable more precise etiologically adapted treatment strategies for ALI.

Therapeutic strategies targeting MQC provide a multifaceted framework for mitigating ALI by directly addressing mitochondrial dysfunction, a central driver of hepatocellular damage. The approaches discussed in the present review, including small-molecule drugs, natural compounds, gene- and cell-based therapies, and emerging bioengineering technologies, converge on the shared objective of preserving or restoring mitochondrial homeostasis in stressed hepatocytes. These strategies can reduce oxidative stress, remove or replace damaged mitochondria, and restore bioenergetic function through coordinated regulation of mitophagy, mitochondrial dynamics and mitochondrial biogenesis.

An effective MQC-targeted intervention is unlikely to depend on the simple activation of mitochondrial turnover. Instead, it requires precise context-dependent modulation according to the etiology of the injury, disease stage and balance among individual MQC modules (52,85). However, whether these strategies can be translated into clinical practice depends on several unresolved issues, including safety, delivery, therapeutic timing, biomarkers and patient heterogeneity. The translational challenges are discussed in detail in the current review.

Despite encouraging preclinical findings, several barriers have limited the clinical translation of MQC-targeted therapies for ALI. First, most candidate interventions have only been validated in cell-based or animal models; human trials specifically designed to assess MQC modulation are scarce (52,84). Second, safety concerns must be carefully considered because excessive activation or inhibition of MQC may disrupt physiological mitochondrial turnover and impair hepatocyte metabolism (85). Third, efficient delivery to injured hepatocytes remains a challenge, particularly in gene-based strategies, mitochondrial transplantation and nanocarrier systems (108–110). Fourth, the therapeutic window is likely narrow because mitophagy, mitochondrial dynamics and mitochondrial biogenesis exhibit distinct temporal patterns during the progression of ALI. Fifth, reliable biomarkers capable of monitoring mitochondrial damage, mitophagic flux and biogenic activity in patients are still lacking. Finally, patient heterogeneity in etiology, injury severity, comorbidities and baseline mitochondrial function may strongly influence therapeutic responses. These limitations suggest that MQC-targeted therapies require etiologically stratified, time-sensitive and biomarker-guided development before clinical application. Representative MQC-targeted therapeutic candidates, their molecular targets, experimental models and translational statuses are summarized in Table II.