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In lower organisms such as yeast, silent information regulator 2 (Sir2), a NAD-dependent deacetylase, links the metabolic activity of yeast to its aging phenotype. Mammals have seven Sir2 homologs, SIRT1-7, which have conserved NAD-dependent deacetylase and/or ADP-ribosyltransferase activities. Although mammalian sirtuins have not been shown to regulate life span, they affect various cellular ... read moreprocesses including cell survival and metabolism. In this project, we study SIRT5, a mitochondrial sirtuin previously shown to regulate carbamoyl phosphate synthetase 1 (CPS1), the rate-limiting enzyme of the urea cycle, via reversible acetylation. Our aim was to determine whether SIRT5 regulates cholesterol metabolism. We show that SIRT5 KO mice on high cholesterol diet had lower levels of cholesterol and triglycerides in their serum, but this phenotype did not repeat in a following trial. Also, we show that expression levels of select genes in mitochondrial oxidative phosphorylation are upregulated in the heart of SIRT5 KO mice. Our findings highlight the importance for future studies in uncovering new functions of SIRT5.read less
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