title: SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria.
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.
authors.affiliation: Institute of Genetic Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, 1064 Ross, 720 Rutland Avenue, Baltimore, MD 21205, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Onyango
authors.forename: Ivana
authors.initials: I
authors.lastname: Celic
authors.forename: J Michael
authors.initials: JM
authors.lastname: McCaffery
authors.forename: Jef D
authors.initials: JD
authors.lastname: Boeke
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Feinberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D003001:Cloning, Molecular; D019295:Computational Biology; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D006655:Histone Deacetylases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D056566:Sirtuin 3; D037761:Sirtuins; D014018:Tissue Distribution
chemical_list: D018076:DNA, Complementary; D024101:Mitochondrial Proteins; D011993:Recombinant Fusion Proteins; C466093:SIRT3 protein, human; D056566:Sirtuin 3; D037761:Sirtuins; D006655:Histone Deacetylases