Metabolic Dysfunction-Associated Steatotic Liver Disease and Mitochondrial Quality Control: From Laboratory to...

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 1.66 billion people globally. This metabolic disorder shows strong connections with mitochondrial dysfunction and disrupted mitochondrial quality control (MQC) processes. Our review systematically analyzes the molecular mechanisms underlying the relationship between MQC and MASLD development. Research evidence indicates that impaired MQC regulation worsens three key pathological conditions: it intensifies liver fat accumulation, increases oxidative damage, and promotes inflammatory cell death through activating inflammatory signaling pathways, boosting reactive oxygen species generation, and triggering programmed cell death in hepatocytes. Current pharmacological interventions have shown mixed effects. Metformin, resveratrol, and empagliflozin have moderating effects on MQC homeostasis in experimental models, but their clinical application remains limited. The review further predicts two key systemic impacts of MASLD: it amplifies cardiovascular disease risk through links between organ systems, and it highlights the need to develop targeted regulation of the gut microbiota. Three major research challenges require urgent attention: first, clarifying the complex interactions between different MQC pathways; second, establishing clinical effectiveness through human trials; third, bridging the gap between laboratory findings and practical medical interventions. These priorities highlight the need for coordinated multidisciplinary research efforts to address this growing public health challenge.