Exercise and dietary interventions in the regulation of hepatic mitophagy and liver recovery (Review)

The high metabolic demand of the liver renders it dependent on mitophagy for mitochondrial quality control. While exercise and nutritional interventions are known to influence hepatic mitophagy, the precise regulatory mechanisms remain incompletely understood. Mitophagy in the liver is influenced by a combination of exercise-related parameters, dietary factors and sex-specific biological factors. Drawing from 19 animal studies published between 2016 and 2026, the present narrative review examines how different exercise modalities and dietary interventions regulate hepatic mitophagy. Among models of obesity and metabolic dysfunction, structured endurance training and higher-intensity exercise protocols yield better capacity to re-establish coordinated mitochondrial quality control than voluntary or low-intensity physical activity protocols. Notably, a single bout of exercise can produce a transient elevation in mitophagic flux, whereas sustained training over time expands mitophagy capacity without necessarily maintaining heightened flux at rest. Moderate-intensity continuous training more effectively restores canonical PTEN-induced kinase 1/Parkin-dependent flux, whereas high-intensity interval training favors structural mitochondrial recovery and upstream energetic signaling, although the relative efficacy depends on the model, disease severity and readout assessed. In high-fat or Western dietary settings, mitophagy is often compromised, with exercise producing incomplete recovery unless paired with improved diet or weight loss. These responses are also influenced by sex differences: Females tend to maintain higher intrinsic mitochondrial quality with less inducible mitophagy, whereas males exhibit a greater reliance on exercise-induced activation of mitophagy. Paternal and maternal developmental programming has also emerged as an important modulator of mitophagy induction. In conclusion, mitophagy in the liver is modified by different exercise and dietary interventions in a manner that is further conditioned by sex and developmental history.