Abstract 210: Progressive Mitochondrial Protein Acetylation and Microsteatosis is Associated with Diastolic Dysfunction in a Hypertrophic Cardiomyopathy Model

We tested the hypothesis that increased mitochondrial protein acetylation is associated with impaired fatty acid metabolismand diastolic dysfunction in Friedreich’s Ataxia (FRDA). FRDA results from deficiency of the mitochondrial protein, frataxin(FXN), and causes hypertrophic cardiomyopathy. FRDA hearts show decreased ATP production. We previously showed that FXN loss results in loss of activity of the NAD+-dependent mitochondrial deacetylase, sirtuin3 ( SIRT3), and cardiac mitochondrial protein hyperacetylation in a mouse model of FRDA. Long-chain and medium chain acyl CoA dehydrogenases(LCAD, MCAD) are targets of SIRT3, suggesting that abnormal acetylation may alter fatty acid metabolism. A cardiac specific mouse model with conditional deletion of FXN in heart and skeletal muscle (FXN MCK-Cre-/-) was compared to healthy controls (FXNfl/fl). Mice underwent echocardiogram and left heart catheterization in vivo at age 30 and 65 days. Heart lysate was examined for overall lysine acetylation at ages 30, ...