Abstract 14989: SIRT3 Deficiency Impairs Mitochondrial and Contractile Function in the Heart

Sirtuin 3 (SIRT3) is a mitochondrial NAD+-dependent deacetylase which is highly expressed in the heart, and which increases mitochondrial ATP production. In rodent models of heart failure reduced SIRT3 expression is associated with mitochondrial dysfunction. Thus, we hypothesized that lack of SIRT3 may impair mitochondrial and contractile function in the heart. In isolated working hearts, developed pressure (-17%), cardiac power (-28%) and MVO2 (-17%) were significantly decreased in mice lacking SIRT3 (SIRT3-/-). Palmitate oxidation (-33%) and glucose oxidation (-39%) were decreased while rates of glycolysis (+40%; all p