Targeting Mitochondrial Dysfunction for the Prevention and Treatment of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disorder worldwide, with its prevalence closely linked to metabolic comorbidities. Mitochondrial dysfunction, a central mechanism underlying metabolic dysregulation, is recognized as a critical driver of NAFLD pathogenesis. This review systematically delineates the molecular mechanisms of mitochondrial dysfunction in NAFLD, encompassing multidimensional networks such as mitochondrial dynamics imbalance, oxidative stress, aberrant metabolic signaling, and inter-organelle crosstalk. Furthermore, we propose novel mitochondrial-targeted therapeutic strategies for NAFLD, including restoration of energy metabolism and mitigation of oxidative damage through antioxidant interventions, modulation of mitochondrial dynamics, and activation of autophagy. Finally, we summarize current research limitations and future directions in targeting mitochondrial dysfunction. By integrating existing evidence, this review establishes a robust theoretical framework for mitochondrial-targeted therapies in NAFLD, offering innovative clinical approaches and a transformative paradigm for addressing the global burden of metabolic liver diseases.