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REVIEW article

Front. Mol. Biosci.

Sec. Mitochondria in Physiology and Disease

Roles of Mitochondrial Complexes in Non-Alcoholic Fatty Liver Disease

  • 1. Shenzhen Longgang District Orthopedic Hospital, Shenzhen, China

  • 2. Jilin University, Changchun, China

  • 3. Xi'an Medical College, Xian, China

  • 4. Peking University, Beijing, China

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Abstract

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.

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Keywords

Energy Metabolism, Lipid Metabolism, Mitochondrial Complexes, Non-alcoholic fatty liver disease (NAFLD), redox homeostasis

Received

22 November 2025

Accepted

13 January 2026

Copyright

© 2026 wang, wang, ning and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Dexin Li

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