February 6, 2019

Dr. Dao-Fu Dai received a five-year NIH K08 award entitled “The role of energy sensor signaling in mitochondrial cardiomyopathy” from the National Heart, Lung and Blood Institute. This study will investigate the strategy of increasing intracellular NAD⁺ levels by supplementation of Nicotinamide Riboside (NR) and overexpression of sirtuin-1 to enhance the NAD⁺-dependent sirt1 deacetylase activity in mitochondrial cardiomyopathy. The studies will use a mouse model of complex I Ndufs4 subunit deficiency and human induced pluripotent stem cell-derived cardiomyocytes with mitochondrial complex I Ndufs4 or Ndufs2 deficiency. Activation of NAD⁺-dependent sirt1 is expected to deacetylate and activate several downstream regulators, including PGC-1α and several cardiac ion channels, such as the sodium channel Nav1.5, thereby rescuing energetic failure and arrhythmia observed in mitochondrial complex I cardiomyopathy.