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Review
. 2025 Jun 27:13:1614940.
doi: 10.3389/fcell.2025.1614940. eCollection 2025.

Mechanism and regulation of mitophagy in liver diseases: a review

Sen Liu  1   2 , Libo Wang  2 , Liuyang Zhu  3 , Tianyu Zhao  2 , Pinsheng Han  4 , Fengying Yan  2 , Xiaoliang Wang  2 , Chunli Li  1   5 , Ze Wang  2 , Bao-Feng Yang  1   6
Affiliations
Review

Mechanism and regulation of mitophagy in liver diseases: a review

Sen Liu et al. Front Cell Dev Biol. .

Abstract

Mitochondria are vital for the proper operation of healthy eukaryotic cells. Mitophagy, a specialized form of autophagy that targets damaged or surplus mitochondria, plays a key role in both the normal functioning and disease-related processes within the liver. This review aims to explore the main mechanisms underlying the initiation of mitophagy and its importance in various liver conditions, such as alcoholic liver disease, drug-induced liver injury, non-alcoholic fatty liver disease, viral hepatitis, and cancer. Gaining insight into these mechanisms can help overcome the obstacles related to harnessing mitophagy as a therapeutic strategy in clinical practice.

Keywords: DILI; NAFLD; liver disease; mitochondria; mitophagy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Parkin-dependent and Parkin-independent mitophagy. Under healthy mitochondrial conditions, PINK1 is anchored at the OMM and continuously imported from the cytosol to the IMM. It is then cleaved by mitochondrial proteases and translocated back to the cytosol. Once mitochondria are damaged under stress accompanied by MMP loss, the import of PINK1 is abolished; therefore, it accumulates on the OMM, leading to the recruitment and phosphorylation of Parkin. Subsequently, Parkin polyubiquitinates OMM proteins to form ubiquitin chains that bind to cargo receptors. These receptors interact with LC3 to form double-membrane mitophagosomes. Mitophagosomes fuse with lysosomes to form mitolysosomes, which then degrade damaged mitochondria.
FIGURE 2
FIGURE 2
Summary of the role of mitophagy in liver disease. Mitophagy occurs in various liver diseases via distinct mitophagy regulators.
See this image and copyright information in PMC

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