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.
Publication types
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
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*
-
Histone Deacetylases / isolation & purification
-
Histone Deacetylases / metabolism*
-
Humans
-
Mitochondria / enzymology
-
Mitochondrial Proteins / genetics*
-
Mitochondrial Proteins / isolation & purification
-
Mitochondrial Proteins / metabolism*
-
Molecular Sequence Data
-
Recombinant Fusion Proteins / genetics
-
Recombinant Fusion Proteins / metabolism
-
Sequence Homology, Amino Acid
-
Sirtuin 3
-
Sirtuins
-
Tissue Distribution
Substances
-
DNA, Complementary
-
Mitochondrial Proteins
-
Recombinant Fusion Proteins
-
SIRT3 protein, human
-
Sirtuin 3
-
Sirtuins
-
Histone Deacetylases