1. SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria
- Author
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Onyango, Patrick, Celic, Ivana, McCaffery, J. Michael, Boeke, Jef D., and Feinberg, Andrew P.
- Subjects
Genetic research ,Homology (Biology) -- Genetic aspects ,Homology (Biology) -- Physiological aspects ,Yeast fungi -- Genetic aspects ,Yeast fungi -- Physiological aspects ,Science and technology - 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 NA[D.sup.+]-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.
- Published
- 2002