Cardiomyocyte lncRNA Cpat maintains cardiac homeostasis and mitochondria function by targeting citrate synthase acetylation.

Summary

This mechanistic study identifies a cardiomyocyte-enriched lncRNA (Cpat) that preserves mitochondrial TCA cycle flux by inhibiting GCN5-mediated citrate synthase acetylation and stabilizing the MDH2-CS-ACO2 complex. Cpat protects against myocardial injury in sepsis-induced cardiomyopathy, highlighting a metabolic RNA-based therapeutic target.

Key Findings

• Identification of cardiomyocyte-enriched lncRNA Cpat as a regulator of mitochondrial TCA cycle flux.
• Cpat stabilizes the MDH2–CS–ACO2 complex by inhibiting GCN5-mediated acetylation of citrate synthase.
• Cpat attenuates myocardial injury in sepsis-induced cardiomyopathy, suggesting therapeutic potential.

Clinical Implications

Although preclinical, targeting Cpat or the GCN5–citrate synthase acetylation axis could inform future therapies to prevent or treat sepsis-induced cardiac dysfunction by restoring mitochondrial metabolism.

Limitations

• Preclinical study without human validation or clinical endpoints.
• Translational challenges for lncRNA delivery, specificity, and safety remain unresolved.

Future Directions

Test Cpat modulation in large-animal sepsis models; evaluate druggable approaches to inhibit GCN5–CS acetylation; assess cardiac and systemic outcomes in early-phase clinical studies.