Sepsis-induced cardiomyopathy (SICM) is a prevalent cardiac complication of sepsis that is characterized by inflammatory dysregulation, mitochondrial dysfunction, metabolic disturbance, and changes in the myocardial microenvironment. Mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) is a mitochondrial-derived microprotein with metabolic regulatory and stress-responsive properties. Existing studies have linked MOTS-c to AMP-activated protein kinase-related energy metabolism, antioxidant responses, inflammatory restraint, endothelial and microvascular protection, and mitochondrial quality control. These processes are relevant to SICM; however, there is limited direct SICM-specific evidence for MOTS-c, and several proposed mechanisms, such as stress-responsive nuclear signaling, have been established primarily in non-SICM settings. This review summarizes the biological characteristics and stress-responsive regulation of MOTS-c, evaluates its potential involvement in pathological processes related to SICM, and distinguishes direct SICM evidence from findings extrapolated from other cardiovascular, metabolic, and inflammatory disease models. We also discuss the exploratory value and current limitations of MOTS-c as a stress-related adjunctive biomarker and potential therapeutic candidate, with particular attention to biomarker specificity, post-treatment efficacy, target-cell mechanisms, and pharmacokinetic or biodistribution issues under septic conditions. Overall, MOTS-c represents a plausible but insufficiently validated molecule in SICM research, and its translational relevance will depend on disease-specific mechanistic and pharmacological validation.
Zeze Zhao, Wei Chen, Xiaoqian Zheng et al.· European Journal of Pharmaco...· 0 citations
Sepsis-induced cardiomyopathy (SICM) is a common and severe complication of sepsis that contributes substantially to circulatory instability, organ dysfunction, and adverse clinical outcomes. Mitochondrial dysfunction and metabolic reprogramming have emerged as central mechanisms underlying its pathogenesis. Because the adult myocardium depends heavily on mitochondrial lipid metabolism for continuous energy production, disruption of lipid metabolic homeostasis may critically impair myocardial bioenergetics and stress adaptation during sepsis.
Current evidence indicates that SICM is accompanied by extensive abnormalities in mitochondrial lipid metabolism, including impaired fatty acid uptake and oxidation, pathological cardiolipin remodeling, excessive lipid peroxidation, ferroptosis, disrupted lipid droplet–mitochondria interactions, and defective mitochondrial dynamics and quality control. These alterations interact with inflammatory signaling, redox imbalance, and metabolism-associated post-translational modifications, collectively promoting adenosine triphosphate (ATP) depletion, lipotoxicity, oxidative injury, and cardiac dysfunction.
This review summarizes the physiological organization of mitochondrial lipid metabolism in the healthy myocardium and systematically examines the mechanisms responsible for its dysregulation in SICM. Particular emphasis is placed on cardiolipin remodeling and mitochondrial membrane lipid homeostasis as potential links among impaired substrate oxidation, respiratory chain instability, oxidative stress amplification, and myocardial injury. Emerging therapeutic strategies aimed at restoring metabolic flexibility, preserving mitochondrial membrane integrity, limiting lipid peroxidation, and improving mitochondrial quality control are also evaluated. A better understanding of these mechanisms may support earlier recognition of metabolically distinct SICM phenotypes, improve the timing and selection of targeted interventions, and facilitate the development of more precise approaches to reducing sepsis-related cardiac injury and improving patient outcomes.
Wei Chen, Zeze Zhao, Xiaoqian Zheng et al.· Lipids in Health and Disease· 0 citations
