Source: recombinant N-terminal Hexahistidine-tagged SIRT3 amino acids 101-399 purified from E. coli · M_r: 37.0 kDa · The sirtuins represent a distinct class of trichostatin A-insensitive lysyl-deacetylases (class III HDACs) and have been shown to catalyze a reaction that couples lysine deacetylation to the formation of nicotinamide and O-acetyl-ADP-ribose from NAD⁺ and the abstracted acetyl group.^1,2,3 There are seven human sirtuins (SIRTs), which have been designated SIRT 1-7.⁴ SIRT3, is a mitochondrial protein, with its N-terminal 25 amino acid residues responsible for its localization.^5,6 Synthesized as an enzymatically inactive protein, human SIRT3 is activated by a matrix-processing peptidase.⁶ Recently, it was demonstrated that SIRT3 is translocated to the mitochondria from the nucleus during cellular stress or by the overexpression of SIRT3 itself.⁷ In mice, caloric restriction up-regulates SIRT3 expression levels in white and brown adipose tissue (WAT & BAT). Cold exposure also induces SIRT3 in brown adipose tissue (BAT).⁸ The constitutive expression of SIRT3 promotes the expression of PGC-1a, UCP1, and other genes involved in mitochondrial functions, indicating that SIRT3 modulates adaptive thermogenesis in BAT.⁸

1 Imai, S., Armstrong, C.M., Kaeberlein, M., et al. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403 795-800 (2000).

2 Tanner, K.G., Landry, J., Sternglanz, R., et al. Silent information regulator 2 family of NAD-dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose. Proc Natl Acad Sci USA 97(26) 14178-14182 (2000).

3 Tanny, J.C., and Moazed, D. Coupling of histone deacetylation to NAD breakdown by the yeast silencing protein Sir2: Evidence for acetyl transfer from substrate to an NAD breakdown product. Proc Natl Acad Sci USA 98(2) 415-420 (2001).

4 Frye, R.A. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun 273 793-798 (2000).

5 Onyango, P., Celic, I., McCaffery, J.M., et al. SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria. Proc Natl Acad Sci USA 99(21) 13653-13658 (2002).

6 Schwer, B., North, B.J., Frye, R.A., et al. The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase. J Cell Biol 158(4) 647-657 (2002).

7 Scher, M.B., Vaquero, A., and Reinberg, D. SirT3 is a nuclear NAD⁺-dependent histone deacetylase that translocates to the mitochondria upon cellular stress. Genes Dev 21 920-928 (2007).

8 Shi, T., Wang, F., Stieren, E., et al. SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. J Biol Chem 280(14) 13560-13567 (2005).

Shi, T., Wang, F., Stieren, E., et al. SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. J Biol Chem 280(14) 13560-13567 (2005).

Schwer, B., North, B.J., Frye, R.A., et al. The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase. J Cell Biol 158(4) 647-657 (2002).

Frye, R.A. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun 273 793-798 (2000).

Tanner, K.G., Landry, J., Sternglanz, R., et al. Silent information regulator 2 family of NAD-dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose. Proc Natl Acad Sci USA 97(26) 14178-14182 (2000).

Imai, S., Armstrong, C.M., Kaeberlein, M., et al. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403 795-800 (2000).

Tanny, J.C., and Moazed, D. Coupling of histone deacetylation to NAD breakdown by the yeast silencing protein Sir2: Evidence for acetyl transfer from substrate to an NAD breakdown product. Proc Natl Acad Sci USA 98(2) 415-420 (2001).

Scher, M.B., Vaquero, A., and Reinberg, D. SirT3 is a nuclear NAD⁺-dependent histone deacetylase that translocates to the mitochondria upon cellular stress. Genes Dev 21 920-928 (2007).

Onyango, P., Celic, I., McCaffery, J.M., et al. SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria. Proc Natl Acad Sci USA 99(21) 13653-13658 (2002).

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