Progressive mitochondrial protein lysine acetylation and heart failure in a model of Friedreich’s ataxia cardiomyopathy

Stram AR, Wagner GR, Fogler BD, Pride PM, Hirschey MD, Payne RM (2017). PLoS ONE 12(5): e0178354. doi:10.1371/journal.pone.0178354

Acetylation was temporally progressive and paralleled evolution of heart failure in the FXN KO model. Increased acetylation preceded detectable abnormalities in cardiac function and progressed rapidly with age in the FXN KO mouse. Acetylation was also associated with cardiac fibrosis, mitochondrial damage, impaired fat metabolism, and diastolic and systolic dysfunction leading to heart failure. There was a strong inverse correlation between level of protein acetylation and heart function.
These results demonstrate a close relationship between mitochondrial protein acetylation, physiologic dysfunction and metabolic disruption in FRDA hypertrophic cardiomyopathy and suggest that abnormal acetylation contributes to the pathophysiology of heart disease in FRDA. Mitochondrial protein acetylation may represent a therapeutic target for early intervention.


 Progressive mitochondrial protein lysine acetylation and heart failure in a model of Friedreich’s ataxia cardiomyopathy