MOTS-c in sepsis-induced cardiomyopathy: Mechanisms and translational potential.
MOTS-c may have potential relevance in sepsis-induced cardiomyopathy, but more direct evidence is needed to validate its role.
Where it sits
this study against the rest of the mots-c corpusSummary and findings
This review discusses the potential role of MOTS-c in sepsis-induced cardiomyopathy (SICM), a condition characterized by inflammatory and metabolic disturbances. It evaluates existing evidence linking MOTS-c to various biological processes relevant to SICM. The review highlights the need for more direct evidence to support the involvement of MOTS-c in SICM.
Abstract
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.