Roles of mitochondrial complexes in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a mitochondrial-driven metabolic disorder, yet the specific contributions of individual mitochondrial respiratory chain complexes remain poorly defined. In particular, inconsistent alterations in complexes I-V have been reported across different NAFLD models, representing a critical knowledge gap. Here, we systematically reviewed in vivo and in vitro studies to evaluate changes in mitochondrial complexes I-V during NAFLD progression. Overall, NAFLD is commonly associated with reduced complex activity, impaired mitochondrial respiration, and increased reactive oxygen species production. Notably, a subset of studies reported enhanced complex activity and respiration, suggesting context-dependent mitochondrial adaptations. This synthesis clarifies divergent findings and highlights mitochondrial respiratory complexes as dynamic and therapeutically relevant targets for future NAFLD intervention strategies.