Loss of mitochondrial pyruvate transport initiates cardiac glycogen accumulation and heart failure.

ABSTRACT: Heart failure involves metabolic alterations including increased glycolysis despite unchanged or decreased glucose oxidation. The mitochondrial pyruvate carrier (MPC) regulates pyruvate entry into the mitochondrial matrix, and cardiac deletion of the MPC in mice causes heart failure. How MPC deletion results in heart failure is unknown. We performed targeted metabolomics and isotope tracing in wildtype (fl/fl) and cardiac-specific Mpc2-/- (CS-Mpc2-/-) hearts after in vivo injection of U-¹³C-glucose. Failing CS-Mpc2-/- hearts contained normal levels of ATP and phosphocreatine, yet these hearts displayed increased enrichment from U-¹³C-glucose and increased glycolytic metabolite pool sizes. ¹³C enrichment and pool size was also increased for the glycogen inte

SUBMITTER: Weiss RC 

PROVIDER: S-EPMC11185624 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature