Molecular mechanisms of hepatic lipid metabolism disorders: Focus on mitochondrial quality control

Abstract

Alcohol‐associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are the two predominant forms of chronic liver disease worldwide. Regardless of alcohol consumption, patients with NAFLD and ALD exhibit disturbances in lipid metabolism, progressing from simple steatosis to steatohepatitis, fibrosis, and ultimately cirrhosis. The precise mechanisms underlying the pathogenesis of NAFLD and ALD remain unclear. However, numerous studies have highlighted mitochondrial dysfunction as a hallmark of both diseases. Beyond their canonical metabolic function, mitochondria could influence hepatocytes through oxidative stress, intracellular signaling transduction, inflammation, and cell death, all of which are regulated by the mitochondrial quality control (MQC) system. Abnormalities in MQC, including defective mitophagy, erroneous mitochondrial dynamics, and delayed biogenesis, comprise mitochondrial morphological structure, function, and lifespan, resulting in hepatocyte damage. This review explores the involvement of MQC in the pathogenesis of NAFLD and ALD and identifies promising therapeutic targets aimed at enhancing MQC, potentially alleviating metabolic liver disease.