In cardiac hypertrophy (abnormal enlargement of the heart muscle), metabolic reserves in the heart are depleted, which contributes to the development of heart failure.
The primary energy source in the heart relies on fatty acid oxidation within the mitochondria, the cell's energy powerhouse.
‘Heart failure is a condition in which the heart’s muscle becomes weakened after a heart attack or high blood pressure and loses its ability to pump enough blood to supply the body’s needs.’
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.