Regulating Cardiac Energy Metabolism and Bioenergetics by Targeting the DNA Damage Repair Protein BRCA1

Abstract

Alterations in cardiac energy production and substrate metabolism are critical to the severity of ischemic injury and the clinical course of heart failure. We have previously shown that the tumor suppressor BRCA1 functions as a key gatekeeper of cardiac structure and function. Given that in cancer cells, the BRCA1 C-terminal domain directly binds and sequesters acetyl-CoA carboxylase (ACC) thereby inhibiting fatty acid synthesis, we hypothesized that the cardioprotective effects of BRCA1 may be mediated in part via adjustments in cardiac bioenergetics.