Mitochondrial regulation of lactylation in sepsis-induced cardiomyopathy

Sepsis-induced cardiomyopathy (SICM) is a life-threatening complication of sepsis that is characterized by acute cardiac dysfunction and is associated with high mortality. Despite advances in detection techniques that have improved the identification of myocardial abnormalities, the link between these findings and effective therapeutic strategies remains poorly defined. Mitochondrial dysfunction-through its roles in metabolic reprogramming, oxidative stress, and calcium dysregulation-has emerged as a central feature and putative driver of SICM. Recently, lactylation, a lactate-derived posttranslational modification, has been identified as a key mechanism amplifying inflammatory and metabolic dysfunction under these conditions. However, a comprehensive understanding of how mitochondrial dysregulation is mechanistically linked to lactylation and how this axis contributes to the progression of SICM is still lacking. This review aims to synthesize current evidence on the mitochondrial regulation of lactylation in SICM, elucidate the underlying molecular pathways, and evaluate potential therapeutic interventions targeting this axis. By integrating mechanistic insights from preclinical and clinical studies, we seek to bridge the gap between mitochondrial biology and epigenetic metabolic regulation, with the goal of informing future research and improving clinical outcomes in SICM.