NAD-dependent protein deacetylase sirtuin-3, mitochondrial

Definition:

NAD-dependent protein deacetylase. Activates or deactivates mitochondrial target proteins by deacetylating key lysine residues. Known targets include ACSS1, IDH, GDH, SOD2, PDHA1, LCAD, SDHA and the ATP synthase subunit ATP5PO. Contributes to the regulation of the cellular energy metabolism. Important for regulating tissue-specific ATP levels. In response to metabolic stress, deacetylates transcription factor FOXO3 and recruits FOXO3 and mitochondrial RNA polymerase POLRMT to mtDNA to promote mtDNA transcription. Acts as a regulator of ceramide metabolism by mediating deacetylation of ceramide synthases CERS1, CERS2 and CERS6, thereby increasing their activity and promoting mitochondrial ceramide accumulation (By similarity).

References:

[1]. Lei Jin, et al. Crystal structures of human SIRT3 displaying substrate-induced conformational changes. J Biol Chem. 2009 Sep 4;284(36):24394-405. [Content Brief]

[2]. Alessia Peserico, et al. A novel AMPK-dependent FoxO3A-SIRT3 intramitochondrial complex sensing glucose levels. Cell Mol Life Sci. 2013 Jun;70(11):2015-29. [Content Brief]

[3]. Bong-Hyun Ahn, et al. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14447-52. [Content Brief]

[4]. Christine Schlicker, et al. Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. J Mol Biol. 2008 Oct 10;382(3):790-801. [Content Brief]

[5]. Patrick Onyango, et al. SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13653-8. [Content Brief]

[6]. Bjoern Schwer, et al. Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10224-10229. [Content Brief]

[7]. Athanassios Vassilopoulos, et al. SIRT3 deacetylates ATP synthase F1 complex proteins in response to nutrient- and exercise-induced stress. Antioxid Redox Signal. 2014 Aug 1;21(4):551-64. [Content Brief]

[8]. Bjorn Schwer, et al. The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase. J Cell Biol. 2002 Aug 19;158(4):647-57. [Content Brief]

[9]. Sivakama S Bharathi, et al. Sirtuin 3 (SIRT3) protein regulates long-chain acyl-CoA dehydrogenase by deacetylating conserved lysines near the active site. J Biol Chem. 2013 Nov 22;288(47):33837-33847. [Content Brief]

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