Hirschey Matthew D, Shimazu Tadahiro, Capra John A, Pollard Katherine S, Verdin Eric
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94158, USA.
Aging (Albany NY). 2011 Jun;3(6):635-42. doi: 10.18632/aging.100339.
SIRT1 and SIRT3 are NAD+-dependent protein deacetylases that are evolutionarily conserved across mammals. These proteins are located in the cytoplasm/nucleus and mitochondria, respectively. Previous reports demonstrated that human SIRT1 deacetylates Acetyl-CoA Synthase 1 (AceCS1) in the cytoplasm, whereas SIRT3 deacetylates the homologous Acetyl-CoA Synthase 2 (AceCS2) in the mitochondria. We recently showed that 3-hydroxy-3-methylglutaryl CoA synthase 2 (HMGCS2) is deacetylated by SIRT3 in mitochondria, and we demonstrate here that SIRT1 deacetylates the homologous 3-hydroxy-3-methylglutaryl CoA synthase 1 (HMGCS1) in the cytoplasm. This novel pattern of substrate homology between cytoplasmic SIRT1 and mitochondrial SIRT3 suggests that considering evolutionary relationships between the sirtuins and their substrates may help to identify and understand the functions and interactions of this gene family. In this perspective, we take a first step by characterizing the evolutionary history of the sirtuins and these substrate families.
SIRT1和SIRT3是NAD+依赖的蛋白质脱乙酰酶，在哺乳动物中具有进化保守性。这些蛋白质分别位于细胞质/细胞核和线粒体中。先前的报道表明，人类SIRT1可使细胞质中的乙酰辅酶A合成酶1（AceCS1）脱乙酰，而SIRT3可使线粒体中的同源乙酰辅酶A合成酶2（AceCS2）脱乙酰。我们最近发现，3-羟基-3-甲基戊二酰辅酶A合成酶2（HMGCS2）在线粒体中被SIRT3脱乙酰，并且我们在此证明SIRT1可使细胞质中的同源3-羟基-3-甲基戊二酰辅酶A合成酶1（HMGCS1）脱乙酰。细胞质中的SIRT1和线粒体中的SIRT3之间这种新的底物同源模式表明，考虑沉默调节蛋白与其底物之间的进化关系可能有助于识别和理解这个基因家族的功能及相互作用。从这个角度出发，我们通过描述沉默调节蛋白和这些底物家族的进化历史迈出了第一步。
