Mitochondria–immunometabolism in sepsis-induced liver injury: mechanisms, biomarkers, and therapeutic opportunities

Sepsis-induced liver injury (SILI) is a major contributor to organ dysfunction and is closely associated with increased morbidity and mortality in septic patients. However, conventional liver biochemical indicators often fail to capture early mitochondrial and metabolic disturbances that precede overt hepatic dysfunction, limiting timely diagnosis and targeted intervention. Emerging evidence indicates that mitochondrial impairment plays a central role not only in bioenergetic failure but also in coordinating immune–metabolic dysregulation during sepsis. In this review, we critically synthesize current knowledge on mitochondrial injury in SILI, with a focus on its mechanistic links to cellular metabolic reprogramming, redox imbalance, and immune cell dysfunction. We highlight how these interconnected processes contribute to hepatocellular injury and disease progression. Furthermore, we summarize recently identified mitochondrial- and metabolism-associated biomarkers that show promise for earlier detection of liver dysfunction in sepsis. Rather than viewing mitochondrial dysfunction as an isolated event, we emphasize its role as a central mediator connecting metabolic stress and immune responses in the septic liver. This perspective provides a mechanistic basis for understanding disease heterogeneity and may facilitate the development of more precise diagnostic and therapeutic strategies.