Gene Symbol: Sirt3
Description: sirtuin 3
Alias: NAD-dependent protein deacetylase sirtuin-3, mitochondrial, SIRT3L mitochondrial
Species: rat
Products:     Sirt3

Top Publications

  1. Weir H, Murray T, Kehoe P, Love S, VERDIN E, O Neill M, et al. CNS SIRT3 expression is altered by reactive oxygen species and in Alzheimer's disease. PLoS ONE. 2012;7:e48225 pubmed publisher
    ..An essential regulator of mitochondrial function is the deacetylase, sirtuin 3 (SIRT3)...
  2. Michishita E, Park J, Burneskis J, Barrett J, Horikawa I. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell. 2005;16:4623-35 pubmed
    ..and SIRT7 are associated with heterochromatic regions and nucleoli, respectively, where yeast Sir2 functions; 2) SIRT3, SIRT4, and SIRT5 are localized in mitochondria, an organelle that links aging and energy metabolism; 3) cellular ..
  3. Schwer B, Bunkenborg J, Verdin R, Andersen J, Verdin E. Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc Natl Acad Sci U S A. 2006;103:10224-10229 pubmed publisher
    ..AceCS2 is reversibly acetylated at Lys-642 in the active site of the enzyme. The mitochondrial sirtuin SIRT3 interacts with AceCS2 and deacetylates Lys-642 both in vitro and in vivo...
  4. Lombard D, Alt F, Cheng H, Bunkenborg J, Streeper R, Mostoslavsky R, et al. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol. 2007;27:8807-14 pubmed
    ..Studies of the sirtuin SIRT3 have so far been limited to cell culture systems...
  5. Scott I, Webster B, Li J, Sack M. Identification of a molecular component of the mitochondrial acetyltransferase programme: a novel role for GCN5L1. Biochem J. 2012;443:655-61 pubmed publisher
    b>SIRT3 (sirtuin 3) modulates respiration via the deacetylation of lysine residues in electron transport chain proteins. Whether mitochondrial protein acetylation is controlled by a counter-regulatory program has remained elusive...
  6. Grillon J, Johnson K, Kotlo K, Danziger R. Non-histone lysine acetylated proteins in heart failure. Biochim Biophys Acta. 2012;1822:607-14 pubmed publisher
    ..The abundance of NAD-dependent deacetylase sirtuin-3 (Sirt3), a mitochondrial deacetylase was reduced in SS and SHHF failing hearts...
  7. Rangarajan P, Karthikeyan A, Lu J, Ling E, Dheen S. Sirtuin 3 regulates Foxo3a-mediated antioxidant pathway in microglia. Neuroscience. 2015;311:398-414 pubmed publisher
    ..The present study was aimed at investigating the expression and role of Sirtuin 3 (Sirt3), a protein deacetylase which is implicated in regulating cellular ROS levels...
  8. Xu S, Gao Y, Zhang Q, Wei S, Chen Z, Dai X, et al. SIRT1/3 Activation by Resveratrol Attenuates Acute Kidney Injury in a Septic Rat Model. Oxid Med Cell Longev. 2016;2016:7296092 pubmed publisher
    ..Two members of the sirtuin family, SIRT1 and SIRT3, have been implicated in the reversal of mitochondrial damage...
  9. Verdin E. NAD⁺ in aging, metabolism, and neurodegeneration. Science. 2015;350:1208-13 pubmed publisher
    ..Here we review factors that regulate NAD(+) and discuss how supplementation with NAD(+) precursors may represent a new therapeutic opportunity for aging and its associated disorders, particularly neurodegenerative diseases. ..

More Information


  1. Pfleger J, He M, Abdellatif M. Mitochondrial complex II is a source of the reserve respiratory capacity that is regulated by metabolic sensors and promotes cell survival. Cell Death Dis. 2015;6:e1835 pubmed publisher
    ..metabolic sensors, including pyruvate dehydrogenase and AMP-dependent kinase, increases cardiac myocyte RRC via a Sirt3-dependent mechanism...
  2. Chen C, Fu Y, Yu W, Wang W. SIRT3 protects cardiomyocytes from oxidative stress-mediated cell death by activating NF-?B. Biochem Biophys Res Commun. 2013;430:798-803 pubmed publisher
    ..Our previous report demonstrated that mitochondrial SIRT3 plays an essential role in mediating cell survival in cardiac myocytes, and that resveratrol protects ..
  3. Yu W, Zhou H, Lin R, Fu Y, Wang W. Short?term calorie restriction activates SIRT1?4 and ?7 in cardiomyocytes in vivo and in vitro. Mol Med Rep. 2014;9:1218-24 pubmed publisher
    ..patterns in H9c2 cells and rat cardiac tissues, with SIRT1 and 7 predominantly located in the nucleus and SIRT3?5 in the cytoplasm...
  4. Jiang H, Miao Y, Wang Y, Zhao M, Feng Z, Yu X, et al. Aerobic interval training protects against myocardial infarction-induced oxidative injury by enhancing antioxidase system and mitochondrial biosynthesis. Clin Exp Pharmacol Physiol. 2014;41:192-201 pubmed publisher
    ..The anti-oxidative gene sirtuin 3 (SIRT3) and the prosurvival phosphatidylinositol-3 kinase (PI3-K)-protein kinase B (Akt) signalling cascade were also ..
  5. Borengasser S, Lau F, Kang P, Blackburn M, Ronis M, Badger T, et al. Maternal obesity during gestation impairs fatty acid oxidation and mitochondrial SIRT3 expression in rat offspring at weaning. PLoS ONE. 2011;6:e24068 pubmed publisher
    ..Several markers of hepatic mitochondrial function were reduced in offspring of obese dams. These included SIRT3 mRNA (p?=?0.012) and mitochondrial protein content (p?=?0...
  6. Signorile A, Santeramo A, Tamma G, Pellegrino T, D Oria S, Lattanzio P, et al. Mitochondrial cAMP prevents apoptosis modulating Sirt3 protein level and OPA1 processing in cardiac myoblast cells. Biochim Biophys Acta Mol Cell Res. 2017;1864:355-366 pubmed publisher be involved in the mitochondrial dependent apoptosis mechanism, such as optic atrophy 1 (OPA1), sirtuin 3 (Sirt3), deacetylase enzyme and cAMP signal...
  7. Paulin R, Dromparis P, Sutendra G, Gurtu V, Zervopoulos S, Bowers L, et al. Sirtuin 3 deficiency is associated with inhibited mitochondrial function and pulmonary arterial hypertension in rodents and humans. Cell Metab. 2014;20:827-39 pubmed publisher
    ..Mice lacking sirtuin 3 (SIRT3), a mitochondrial deacetylase, have increased acetylation and inhibition of many mitochondrial enzymes and ..
  8. Wu J, Jin Z, Yan L. Redox imbalance and mitochondrial abnormalities in the diabetic lung. Redox Biol. 2017;11:51-59 pubmed publisher
    ..We also measured the protein content of NAD+ dependent enzymes such as sirtuin3 (sirt3) and NAD(P)H: quinone oxidoreductase 1 (NQO1)...
  9. Zeng L, Yang Y, Hu Y, Sun Y, Du Z, Xie Z, et al. Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model. PLoS ONE. 2014;9:e88019 pubmed publisher
    ..b>Sirt3, a mitochondrial NAD+-dependent deacetylase, has been shown to play a crucial role in controlling cellular ..
  10. Dai S, Chen T, Li X, Yue K, Luo P, Yang L, et al. Sirt3 confers protection against neuronal ischemia by inducing autophagy: Involvement of the AMPK-mTOR pathway. Free Radic Biol Med. 2017;108:345-353 pubmed publisher
    Sirtuin3 (Sirt3) is a member of the silent information regulator 2 (Sir2) family of proteins located in mitochondria that influences almost every major aspect of mitochondrial biology, including ATP generation and reactive oxygen species ..
  11. Hokari F, Kawasaki E, Sakai A, Koshinaka K, Sakuma K, Kawanaka K. Muscle contractile activity regulates Sirt3 protein expression in rat skeletal muscles. J Appl Physiol (1985). 2010;109:332-40 pubmed publisher
    b>Sirt3, a member of the sirtuin family, is known to control cellular mitochondrial function...
  12. Jin L, Galonek H, Israelian K, Choy W, Morrison M, Xia Y, et al. Biochemical characterization, localization, and tissue distribution of the longer form of mouse SIRT3. Protein Sci. 2009;18:514-25 pubmed publisher
    b>SIRT3 is a key mitochondrial protein deacetylase proposed to play key roles in regulating mitochondrial metabolism but there has been considerable debate about its actual size, the sequences required for activity, and its subcellular ..
  13. Gurd B, Holloway G, Yoshida Y, Bonen A. In mammalian muscle, SIRT3 is present in mitochondria and not in the nucleus; and SIRT3 is upregulated by chronic muscle contraction in an adenosine monophosphate-activated protein kinase-independent manner. Metabolism. 2012;61:733-41 pubmed publisher
    In selected cell lines, it appears (a) that metabolic stressors induce the translocation of SIRT3 from the nucleus to mitochondria and (b) that SIRT3 may contribute to the regulation of mitochondrial biogenesis and/or fatty acid ..
  14. Koltai E, Zhao Z, Lacza Z, Cselenyák A, Vacz G, Nyakas C, et al. Combined exercise and insulin-like growth factor-1 supplementation induces neurogenesis in old rats, but do not attenuate age-associated DNA damage. Rejuvenation Res. 2011;14:585-96 pubmed publisher
    ..Sirtuin 1 (SIRT1) and SIRT3, as DNA damage-associated lysine deacetylases, were measured, and SIRT1 decreased with aging, resulting in a large ..
  15. Jin L, Wei W, Jiang Y, Peng H, Cai J, Mao C, et al. Crystal structures of human SIRT3 displaying substrate-induced conformational changes. J Biol Chem. 2009;284:24394-405 pubmed publisher
    b>SIRT3 is a major mitochondrial NAD(+)-dependent protein deacetylase playing important roles in regulating mitochondrial metabolism and energy production and has been linked to the beneficial effects of exercise and caloric restriction...
  16. Rardin M, Newman J, Held J, Cusack M, Sorensen D, Li B, et al. Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways. Proc Natl Acad Sci U S A. 2013;110:6601-6 pubmed publisher
    ..Sirtuin 3 (SIRT3) is an NAD(+)-dependent mitochondrial protein deacetylase that has been shown to regulate a limited number of ..
  17. Guo X, Yan F, Shan X, Li J, Yang Y, Zhang J, et al. SIRT3 inhibits Ang II-induced transdifferentiation of cardiac fibroblasts through ?-catenin/PPAR-? signaling. Life Sci. 2017;186:111-117 pubmed publisher
    ..Sirtuin3 (SIRT3) has been believed to protect against cardiac fibrosis...
  18. Caton P, Richardson S, Kieswich J, Bugliani M, Holland M, Marchetti P, et al. Sirtuin 3 regulates mouse pancreatic beta cell function and is suppressed in pancreatic islets isolated from human type 2 diabetic patients. Diabetologia. 2013;56:1068-77 pubmed publisher
    ..are key factors mediating pancreatic beta cell impairment in type 2 diabetes, we investigated the role of SIRT3 in the maintenance of beta cell function and mass in type 2 diabetes...
  19. Wang Q, Li L, Li C, Pei Z, Zhou M, Li N. SIRT3 protects cells from hypoxia via PGC-1α- and MnSOD-dependent pathways. Neuroscience. 2015;286:109-21 pubmed publisher
    Reports suggest that silent information regulation 2 homolog 3 (SIRT3) protects cardiomyocytes from oxidative stress-mediated death...
  20. Claycombe K, Roemmich J, Johnson L, Vomhof DeKrey E, Johnson W. Skeletal muscle Sirt3 expression and mitochondrial respiration are regulated by a prenatal low-protein diet. J Nutr Biochem. 2015;26:184-9 pubmed publisher
    ..muscle mitochondrial function, particularly reduction in expression of mitochondrial protein sirtuin protein 3 (Sirt3) contributes to development of T2DM by reducing mitochondrial respiration...
  21. Huang W, Huang Y, Huang R, Huang C, Wang W, Gu J, et al. SIRT3 Expression Decreases with Reactive Oxygen Species Generation in Rat Cortical Neurons during Early Brain Injury Induced by Experimental Subarachnoid Hemorrhage. Biomed Res Int. 2016;2016:8263926 pubmed publisher
    Sirtuin3 (SIRT3) is an important protein deacetylase which predominantly presents in mitochondria and exhibits broad bioactivities including regulating energy metabolism and counteracting inflammatory effect...
  22. Zhang H, Ma X, Wu L, Zhao Y, Zhang P, Zhang Y, et al. Sirtuin-3 (SIRT3) protects pancreatic ?-cells from endoplasmic reticulum (ER) stress-induced apoptosis and dysfunction. Mol Cell Biochem. 2016;420:95-106 pubmed publisher
    ..In this study, we hypothesized that NAD-dependent deacetylase sirtuin-3 (SIRT3), an important regulator of cell metabolism, protects pancreatic ?-cells from ER stress-mediated apoptosis...
  23. Yue Z, Ma Y, You J, Li Z, Ding Y, He P, et al. NMNAT3 is involved in the protective effect of SIRT3 in Ang II-induced cardiac hypertrophy. Exp Cell Res. 2016;347:261-73 pubmed publisher
    ..b>SIRT3, a mitochondria-localized sirtuin, regulates global mitochondrial lysine acetylation and preserves mitochondrial ..
  24. Zeng Y, Yang K, Wang F, Zhou L, Hu Y, Tang M, et al. The glucagon like peptide 1 analogue, exendin-4, attenuates oxidative stress-induced retinal cell death in early diabetic rats through promoting Sirt1 and Sirt3 expression. Exp Eye Res. 2016;151:203-11 pubmed publisher
    ..In the retinas of early-stage diabetic rats, the expressions of Sirt1 and Sirt3 were also found to be significantly decreased, and both were back to normal levels after intravitreal injection of ..
  25. Cheung K, Cole L, Xiang B, Chen K, Ma X, Myal Y, et al. Sirtuin-3 (SIRT3) Protein Attenuates Doxorubicin-induced Oxidative Stress and Improves Mitochondrial Respiration in H9c2 Cardiomyocytes. J Biol Chem. 2015;290:10981-93 pubmed publisher
    ..Sirtuin-3 (SIRT3) is a class III lysine deacetylase that is localized to the mitochondria and regulates mitochondrial respiration ..
  26. Valdecantos M, Perez Matute P, Gonzalez Muniesa P, Prieto Hontoria P, Moreno Aliaga M, Martinez J. Lipoic acid improves mitochondrial function in nonalcoholic steatosis through the stimulation of sirtuin 1 and sirtuin 3. Obesity (Silver Spring). 2012;20:1974-83 pubmed publisher
    ..001- P < 0.01) through the stimulation of SIRT3 and SIRT1 (P < 0.001)...
  27. Qin B, Panickar K, Anderson R. Cinnamon polyphenols regulate S100?, sirtuins, and neuroactive proteins in rat C6 glioma cells. Nutrition. 2014;30:210-7 pubmed publisher
  28. Rato L, Duarte A, Tomás G, Santos M, Moreira P, Socorro S, et al. Pre-diabetes alters testicular PGC1-?/SIRT3 axis modulating mitochondrial bioenergetics and oxidative stress. Biochim Biophys Acta. 2014;1837:335-44 pubmed publisher
    ..Peroxisome proliferator-activated receptor ? coactivator 1 ? (PGC-1?) and Sirtuin 3 (Sirt3) are pivotal in mitochondrial function...
  29. You J, Yue Z, Chen S, Chen Y, Lu X, Zhang X, et al. Receptor-interacting Protein 140 represses Sirtuin 3 to facilitate hypertrophy, mitochondrial dysfunction and energy metabolic dysfunction in cardiomyocytes. Acta Physiol (Oxf). 2017;220:58-71 pubmed publisher
    ..This study revealed that RIP140 repressed Sirtuin 3 (SIRT3), a mitochondrial deacetylase that plays an important role in regulating cardiac function...
  30. Macconi D, Perico L, Longaretti L, Morigi M, Cassis P, Buelli S, et al. Sirtuin3 Dysfunction Is the Key Determinant of Skeletal Muscle Insulin Resistance by Angiotensin II. PLoS ONE. 2015;10:e0127172 pubmed publisher
    ..The present results also highlight Sirtuin3 as a therapeutic target for the insulin-sensitizing effects of acetyl-L-carnitine. ..
  31. Klishadi M, Zarei F, Hejazian S, Moradi A, Hemati M, Safari F. Losartan protects the heart against ischemia reperfusion injury: sirtuin3 involvement. J Pharm Pharm Sci. 2015;18:112-23 pubmed
    Sirtuin-3 (SIRT3) deacetylase protects the heart against oxidative stress via survival factors upregulation...
  32. Guan X, Hong X, Zhao N, Liu X, Xiao Y, Chen T, et al. CD38 promotes angiotensin II-induced cardiac hypertrophy. J Cell Mol Med. 2017;21:1492-1502 pubmed publisher
    ..In addition, the expression of SIRT3 was elevated in CD38 knockdown H9c2 cells, in which SIRT3 may further activate the FOXO3 antioxidant pathway...
  33. Nakamura Y, Ogura M, Tanaka D, Inagaki N. Localization of mouse mitochondrial SIRT proteins: shift of SIRT3 to nucleus by co-expression with SIRT5. Biochem Biophys Res Commun. 2008;366:174-9 pubmed
    Yeast silent information regulator 2 (SIR2) is involved in extension of yeast longevity by calorie restriction, and SIRT3, SIRT4, and SIRT5 are mammalian homologs of SIR2 localized in mitochondria...
  34. Zeng Z, Yang Y, Dai X, Xu S, Li T, Zhang Q, et al. Polydatin ameliorates injury to the small intestine induced by hemorrhagic shock via SIRT3 activation-mediated mitochondrial protection. Expert Opin Ther Targets. 2016;20:645-52 pubmed publisher
    ..To explore the role of SIRT3 and mitochondria in SI injury after HS, and explore SIRT3 as a therapeutic target of PD in HS...
  35. Li T, Li Z, Zhuang X, Fu Y. [Effects of caloric restriction on the oxidative stress injury and the expression of SIRT3 in PC12 cell]. Zhonghua Yi Xue Za Zhi. 2011;91:350-8 pubmed
    To study the regulation effects of CR (caloric restriction) and SIRT3 in the H2O2-induced oxidative stress injury of PC12 cell. The cells were divided into four groups: H2O2, H2O2 + CR, CR and control (high glucose)...
  36. Yang Y, Chen Y, Zhang C, Nimmakayalu M, Ward D, Weissman S. Cloning and characterization of two mouse genes with homology to the yeast Sir2 gene. Genomics. 2000;69:355-69 pubmed
    ..The two mouse genes have completely different genomic structures but were mapped on the same chromosome. It seems that the two mouse proteins, though they have Sir2 conserved domains, may function differently than yeast Sir2p. ..