SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria
P Onyango, I Celic, JM McCaffery… - Proceedings of the …, 2002 - National Acad Sciences
Proceedings of the National Academy of Sciences, 2002•National Acad Sciences
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 …
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 …
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.
National Acad Sciences