GCN5L1 promotes diastolic dysfunction by inhibiting cardiac pyruvate oxidation

Abstract

Alterations in cardiac fuel metabolism underpin the development of heart failure with preserved ejection fraction (HFpEF). Mouse models of HFpEF, in addition to changes in fuel choice, display elevated levels of mitochondrial protein acetylation. Reversal of mitochondrial hyperacetylation restores cardiac bioenergetics and function. In this study, we examined the metabolic mechanisms of diastolic dysfunction in diet induced failing hearts, using a model of constitutively reduced mitochondrial protein acetylation.