In cardiac hypertrophy, metabolic energy reserves in the heart are depleted, which is thought to contribute to the subsequent development of heart failure. The primary energy source in the heart relies on fatty acid oxidation within the mitochondria, the cell's energy powerhouse. In this month's issue of JCI Insight , Daniel Kelly of the Sanford Burnham Prebys Medical Discovery Institute and his coauthors sought to explore how post-translational modification of mitochondrial proteins involved in energy metabolism contributes to the development of heart failure. Using an unbiased screen to look for changes in protein acetylation, the researchers profiled heart tissue from 5 end-stage heart failure patients who went on to receive heart transplants. They found that failing cardiac tissue had increased levels of acetylated mitochondrial proteins. Further, in a mouse model, they detected elevated levels of mitochondrial protein acetylation at the earliest stages of heart failure. As a proof of principle, they showed that increased acetylation of one specific protein, succinate dehydrogenase A, reduced its function in cultured cells. Collectively, their work suggests that mitochondrial protein hyperacetylation may promote the metabolic defects seen in heart failure.
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TITLE: Mitochondrial Protein Hyperacetylation in the Failing Heart
AUTHOR CONTACT: Daniel P. Kelly
Sanford Burnham Prebys Medical Discovery Institute
Email: dkelly@sanfordburnham.org
View this article at: http://insight.jci.org/articles/view/84897
JCI Insight is the newest publication from the American Society of Clinical Investigation, a nonprofit honor organization of physician-scientists. JCI Insight is dedicated to publishing a range of translational biomedical research with an emphasis on rigorous experimental methods and data reporting. All articles published in JCI Insight are freely available at the time of publication. For more information about JCI Insight and all of the latest articles go to http://www.insight.jci.org .
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