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The role and mechanism of action of mitophagy in various liver diseases.

SIGNIFICANCE
Liver disease is one of the biggest threats to public health, affecting as much as 5.5 million people worldwide. Mitochondrial dysfunction is associated with various acute and chronic liver diseases. Mitophagy plays a key role either in the pathogenesis or in maintaining hepatic homeostasis in response to various liver diseases.


RECENT ADVANCES
Significant progress has been achieved to ascertain the causes of liver disease. The conserved pathways for mitochondrial degradation via mitophagy, the deregulation of mitophagy in liver diseases, and pharmacological or genetic maneuvers that alter the mitophagic flux for liver disease treatment have been widely studied but yet to be comprehensively reviewed.


CRITICAL ISSUES
Liver disease is considered a leading cause of mortality globally, causing the heavy burden of disability and the increased health care utilization that needs to be settled urgently. Mitophagy plays an important role in protecting liver from tissue damage. Elaborating mitophagy implicated in the pathogenesis of liver disease, as well as potential therapeutic regimens by targeting mitophagy is of great significance for the understanding and treating of liver disease.


FUTURE DIRECTIONS
This review comprehensively describes the distinct mitophagy signaling pathways and their interplay with various liver diseases. A deeper understanding of how to modulate mitophagy could provide innovative avenues for precise therapy. Future studies based on pharmacologically or genetically targeting mitophagy-relevant factors will uncover the links between intact mitophagic responses and hepatic homeostasis in physiological and pathological settings. This will allow us to overcome obstacles of applying mitophagy as the therapeutic target in clinic.