Protein targets modulated by SIRT3 are being explored using proteomic approaches. Characterization of the role of deacetylation of these targets will then be interogated, in a target function specific manner. We have recently identified a novel mitochondrial deacetylase and the targets fo this enzyme and its role in counterregulaing sirtuin funciton is being explored. Finally, we hyopothesized that acetylation of mitochondrial lysine residues will inhibit binding of xenobiotics metabolites to lysine residues and thereby modulate the mitochondrial catabolism of these potential toxic compounds. In light of the role acetaminophen plays in hepatic injury, we have initially explored this compound and find that the acetylation status of mitochondrial proteins does modulate susceptability to acetaminophen induced liver injury. This finding could have widespread implications in the prevention of hepatotoxicity and may have broader implications for other xenobiotics.
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