RND3 Enhances Cardiac Glucose Metabolism Through Inhibiting ACAT1-Dependent PDHA1 Acetylation and Protects Against Ischemia-Reperfusion Injury
Authors' conclusion
Our results identify RND3 as a novel mitochondria-localized regulator of glucose oxidation that safeguards the heart against I/R injury.
Study context
- Population
- Mice with myocardial I/R injury (left anterior descending coronary artery ligation); human hearts after I/R
- Comparison
- Rnd3cKO vs Rnd3 overexpression
Methodological detailsmurine I/R model, cardiomyocyte-specific knockout and overexpression
- Murine I/R model
- Cardiomyocyte-specific knockout and overexpression
Main finding
As reported in the abstract
- Rnd3cKO: impaired glucose oxidation, compensatory upregulation of fatty acid oxidation, pronounced cardiac dysfunction and increased mortality
- Rnd3cKO hearts: reduced pyruvate/malate-driven complex I respiration and marked uncoupling between glycolysis and the TCA cycle
- RND3 localizes to the mitochondrial matrix and binds ACAT1, disrupting its interaction with PDHA1, promoting PDHA1 acetylation and glucose oxidation
- RND3 expression significantly downregulated in human and murine hearts after I/R
- Loss of RND3 sensitized hearts to I/R injury (reduced phosphocreatine and ATP)
- Cardiac-specific Rnd3 overexpression protected against I/R injury; effect abolished by Pdha1 knockdown
Original publication
RND3 Enhances Cardiac Glucose Metabolism Through Inhibiting ACAT1-Dependent PDHA1 Acetylation and Protects Against Ischemia-Reperfusion Injury. Circulation. Published 11 June 2026. doi:10.
Summarised from the published abstract; every number is checked against it