Mitochondria-focused control networks in fatty liver disease: linking cell cleanup, organ interactions, and gut-liver communication

Metabolic dysfunction-associated steatotic liver disease (MASLD) is driven by a self-amplifying injury loop related to mitochondrial dysfunction.

• Impaired mitochondrial quality control is linked to lipid accumulation and inflammation in the liver.
• Dysregulated mitophagy and mitochondrial fragmentation are associated with worsening MASLD symptoms.
• Abnormal interactions between organelles can lead to calcium overload and increased oxidative stress.
• Gut-derived metabolites, such as short-chain fatty acids and bile acids, may alter mitochondrial energy production.
• Restoring mitochondrial quality control or targeting organelle interactions could potentially alleviate MASLD symptoms.
• Multi-target strategies are necessary for effective clinical interventions due to the complex nature of MASLD.

Simplified