Research Perspective Volume 3, Issue 6 pp 635—642
SIRT1 and SIRT3 Deacetylate Homologous Substrates: AceCS1,2 and HMGCS1,2
- 1 Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94158
- 2 Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94158
- 3 Division of Biostatistics & Institute for Human Genetics, University of California, San Francisco, CA 94107
- 4 Department of Medicine, University of California, San Francisco, CA 94143
Received: June 12, 2011 Accepted: June 18, 2011 Published: June 19, 2011
https://doi.org/10.18632/aging.100339How to Cite
Abstract
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.