Targeted regulation of mitophagy as a potential target for liver fibrosis therapy

Liver fibrosis is a chronic liver condition characterised by impaired liver structure and function due to excessive extracellular matrix deposition, a key pathological feature. Currently, clinical treatment of liver fibrosis primarily focuses on controlling viral hepatitis through antiviral therapy or reducing liver injury by preventing alcohol intake. However, there is a notable lack of specific drugs targeting the pathological processes and mechanisms underlying liver fibrosis. Mitophagy, a selective autophagy process, maintains mitochondrial stability, function, and energy metabolism by eliminating damaged or excess mitochondria. Mitochondrial dysfunction and oxidative stress accelerate hepatic fibrosis, while mitophagy, by preserving mitochondrial quality, can bidirectionally regulate fibrosis progression, either blocking or exacerbating liver damage. Research indicates that increased mitophagy inhibits hepatic stellate cell activation, alleviates mitochondrial oxidative stress and energy metabolism disorders, and mitigates chronic inflammation and extracellular matrix over deposition, making it a potential target for anti-fibrotic therapy. However, some studies suggest excessive mitophagy may worsen fibrosis by impairing hepatic cell regeneration and increasing profibrotic factors like TGF-β. This article examines the role of mitophagy in hepatic fibrosis, exploring its potential applications and novel intervention strategies. It offers potential therapeutic targets and a theoretical foundation for clinical antifibrotic drug development.