# Roles of mitochondrial complexes in non-alcoholic fatty liver disease

## TL;DR

This paper reviews how mitochondrial complexes contribute to non-alcoholic fatty liver disease and identifies key patterns in their activity changes.

## Contribution

The study systematically clarifies inconsistent findings about mitochondrial complex activity in NAFLD.

## Key findings

- NAFLD is often linked to reduced mitochondrial complex activity and increased ROS production.
- Some studies show enhanced complex activity, indicating context-dependent adaptations.
- Mitochondrial respiratory complexes are identified as potential therapeutic targets for NAFLD.

## 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.

Illustration of mitochondrial dysfunction in NAFLD. Shows complexes I to V within a mitochondrion, highlighting impaired and enhanced mitochondrial respiration pathways. A mouse and lab dishes represent in vivo and in vitro studies. Depicts impacts on energy metabolism, lipid metabolism, and ROS, illustrating how reduced complex activity and elevated ROS can lead to inconsistent changes in NAFLD.