SIRT1 and SIRT3 deacetylate homologous substrates: AceCS1,2 and HMGCS1,2.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Hirschey, MD; Shimazu, T; Capra, JA; Pollard, KS; Verdin, E

Published Date

  • June 2011

Published In

Volume / Issue

  • 3 / 6

Start / End Page

  • 635 - 642

PubMed ID

  • 21701047

Pubmed Central ID

  • 21701047

Electronic International Standard Serial Number (EISSN)

  • 1945-4589

Digital Object Identifier (DOI)

  • 10.18632/aging.100339

Language

  • eng

Conference Location

  • United States