KAT6A acetylation mediates metabolic adaptation to growth and mitochondrial metabolism through AMPK

We have previously demonstrated that a ketogenic diet alleviates cardiac pathology under high blood pressure. Here we show that lysine acetyltransferase 6A (KAT6A) is acetylated in the hearts of mice fed a ketogenic diet under hypertension, which enhances its interaction with AMPK regulatory subunits. RNA-sequencing analysis demonstrated that the KAT6A-K815Q acetylation-mimetic mutant stimulates AMPK signaling in cardiomyocytes. Moreover, the KAT6A-K815Q acetylation-mimetic mutant mitigated phenylephrine-induced mitochondrial dysfunction and cardiomyocyte hypertrophy via AMPK activation in vitro. Overall design: Primary rat neonatal cardiomyocytes were transfected with adenovirus-harboring human KAT6A-wild type (WT), -K815R (acetylation-resistant mutant), -K815Q (acetylation-mimetic mutant), or LacZ as a control for two days. Total RNA was isolated using TRIzol. n=3