SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1{alpha}
Language: 
English
Abstract: 

In lower organisms, increased expression of the NAD-dependent deacetylase Sir2 augments lifespan. The mechanism through which this life extension is mediated remains incompletely understood. Here we have examined the cellular effects of overexpression of SIRT1, the closest mammalian ortholog of Sir2. In PC12 cells, increased expression of the NAD-dependent deacetylase SIRT1 reduces cellular oxygen consumption by approximately 25%. We further demonstrate that SIRT1 expression can alter the transcriptional activity of the mitochondrial biogenesis coactivator PGC-1alpha. In addition, SIRT1 and PGC-1alpha directly interact and can be co-immunoprecipitated as a molecular complex. A single amino acid mutation in the putative ADP-ribosyltransferase domain of SIRT1 inhibits the interaction of SIRT1 with PGC-1alpha but does not effect the interaction of SIRT1 with either p53 or Foxo3a. We further show that PGC-1alpha is acetylated in vivo. This acetylation is augmented by treatment with the SIRT1 inhibitor nicotinamide or by expression of the transcriptional coactivator p300. Finally we demonstrate that SIRT1 catalyzes PGC-1alpha deacetylation both in vitro and in vivo. These results provide a direct link between the sirtuins, a family of proteins linked to lifespan determination and PGC-1alpha, a coactivator that regulates cellular metabolism.

Author(s): 
Nemoto, Shino
Fergusson, Maria M.
Finkel, Toren
Item Type: 
Journal Article
Publication Title: 
The Journal of Biological Chemistry
Journal Abbreviation: 
J. Biol. Chem.
Publication Date: 
4/22/2005
Publication Year: 
2005
Pages: 
16456-16460
Volume: 
280
Issue: 
16
ISSN: 
0021-9258
DOI: 
10.1074/jbc.M501485200
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 15716268

Turabian/Chicago Citation

Shino Nemoto, Maria M. Fergusson and Toren Finkel. 4/22/2005. "SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1{alpha}." The Journal of Biological Chemistry 280: 16: 16456-16460. 10.1074/jbc.M501485200.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1074/jbc.M501485200 | issn = 0021-9258 | volume = 280 | pages = 16456-16460 | last = Nemoto | first = Shino | coauthors = Fergusson, Maria M., Finkel, Toren | title = SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1{alpha} | journal = The Journal of Biological Chemistry | date = 4/22/2005 | pmid = | pmc = }} </ref>