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

Patrick Onyango, Ivana Celic, J. Michael McCaffery, Jef D. Boeke, Andrew P. Feinberg

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)13653-13658
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number21
DOIs
StatePublished - Oct 15 2002

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