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PMID: 12374852 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 21 ·2002-10-15 ·Pages 13653-8

Onyango P, Celic I, McCaffery JM, Boeke JD, Feinberg AP

Abstract

The SIR2 (silent information regulator 2) gene family has diverse functions in yeast including gene silencing, DNA repair, cell-cycle progression, and chromosome fidelity in meiosis and aging. Human homologues, termed sirtuins, are highly conserved but are of unknown function. We previously identified a large imprinted gene domain on 11p15.5 and investigated the 11p15.5 sirtuin SIRT3. Although this gene was not imprinted, we found that it is localized to mitochondria, with a mitochondrial targeting signal within a unique N-terminal peptide sequence. The encoded protein was found also to possess NAD(+)-dependent histone deacetylase activity. These results suggest a previously unrecognized organelle for sirtuin function and that the role of SIRT3 in mitochondria involves protein deacetylation.

MeSH Terms
Amino Acid Sequence Animals Base Sequence COS Cells Chromosome Mapping Chromosomes, Human, Pair 11/genetics Cloning, Molecular Computational Biology DNA, Complementary/genetics Gene Expression Histone Deacetylases/genetics,isolation & purification,metabolism Humans Mitochondria/enzymology Mitochondrial Proteins/genetics,isolation & purification,metabolism Molecular Sequence Data Recombinant Fusion Proteins/genetics,metabolism Sequence Homology, Amino Acid Sirtuin 3 Sirtuins Tissue Distribution
Chemicals
DNA, Complementary Mitochondrial Proteins Recombinant Fusion Proteins SIRT3 protein, human Sirtuin 3 Sirtuins Histone Deacetylases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Onyango Patrick
Institute of Genetic Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, 1064 Ross, 720 Rutland Avenue, Baltimore, MD 21205, USA.
Celic Ivana
McCaffery J Michael
Boeke Jef D
Feinberg Andrew P
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.222538099
Published
2002-10-15
Epub
2002-00-08
Pages
13653-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC129731
Subset
IM
Grants
NCI NIH HHS · R37 CA054358-12 · United States
NCI NIH HHS · R37 CA054358 · United States
NIGMS NIH HHS · R01 GM062385 · United States
NCI NIH HHS · R37 CA 54358 · United States
NIGMS NIH HHS · GM 62385 · United States
External Links
PubMed source DOI: 10.1073/pnas.222538099 PMC Full Text View journal details
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