Loss of SIRT2 in cardiomyocytes reduces glycolytic flux via increased acetylation of glycolytic enzymes

Protein lysine acetylation differentially regulates cardiac fatty acid and glucose oxidation. However, its role in controlling glycolysis remains poorly defined. Using pharmacological inhibition and siRNA-mediated knockdown of sirtuin 2 (SIRT2), we demonstrate that loss of SIRT2 increases acetylation of glycolytic enzymes and reduces cardiac glycolytic flux in isolated working hearts and cardiomyocytes, independent of insulin signaling. Our findings reveal an important role of SIRT2-dependent deacetylation in regulating cardiac glycolytic flux.