sirtuin 3


Summary: A sirtuin family member found primarily in MITOCHONDRIA. It is a multifunctional enzyme that contains a NAD-dependent deacetylase activity that is specific for HISTONES and a mono-ADP-ribosyltransferase activity.

Top Publications

  1. Ho L, Wang L, Roth T, Pan Y, VERDIN E, Hsiao E, et al. Sirtuin-3 Promotes Adipogenesis, Osteoclastogenesis, and Bone Loss in Aging Male Mice. Endocrinology. 2017;158:2741-2753 pubmed publisher
    ..These findings identify Sirt3 as an important regulator of adipogenesis and skeletal homeostasis in vivo and identify Sirt3 as a potential target for the treatment of osteoporosis. ..
  2. Sadoshima J. Sirt3 targets mPTP and prevents aging in the heart. Aging (Albany NY). 2011;3:12-3 pubmed
  3. Della Morte D, Dong C, Bartels S, Cabral D, Blanton S, Sacco R, et al. Association of the sirtuin and mitochondrial uncoupling protein genes with carotid intima-media thickness. Transl Res. 2012;160:389-90 pubmed publisher
  4. Kwon S, Seok S, Yau P, Li X, Kemper B, Kemper J. Obesity and aging diminish sirtuin 1 (SIRT1)-mediated deacetylation of SIRT3, leading to hyperacetylation and decreased activity and stability of SIRT3. J Biol Chem. 2017;292:17312-17323 pubmed publisher
    b>Sirtuin 3 (SIRT3) deacetylates and regulates many mitochondrial proteins to maintain health, but its functions are depressed in aging and obesity...
  5. Barger J, Vann J, Cray N, Pugh T, Mastaloudis A, Hester S, et al. Identification of tissue-specific transcriptional markers of caloric restriction in the mouse and their use to evaluate caloric restriction mimetics. Aging Cell. 2017;16:750-760 pubmed publisher
    ..Our findings provide panels of tissue-specific transcriptional markers of CR that can be used to identify novel CRMs, and also represent the first comparative molecular analysis of several potential CRMs in multiple tissues in mammals...
  6. De Matteis S, Granato A, Napolitano R, Molinari C, Valgiusti M, Santini D, et al. Interplay Between SIRT-3, Metabolism and Its Tumor Suppressor Role in Hepatocellular Carcinoma. Dig Dis Sci. 2017;62:1872-1880 pubmed publisher
    ..This evidence suggests a putative bridge role of SIRT-3 between metabolic diseases and HCC. However, further studies are necessary to demonstrate such interconnection. ..
  7. Kenny T, Hart P, Ragazzi M, Sersinghe M, Chipuk J, Sagar M, et al. Selected mitochondrial DNA landscapes activate the SIRT3 axis of the UPRmt to promote metastasis. Oncogene. 2017;36:4393-4404 pubmed publisher
    ..We propose that the ability of selected mtDNA species to activate the UPRmt is a process that is exploited by cancer cells to maintain mitochondrial fitness and facilitate metastasis. ..
  8. Ding Y, Yang H, Wang Y, Chen J, Ji Z, Sun H. Sirtuin 3 is required for osteogenic differentiation through maintenance of PGC-1?-SOD2-mediated regulation of mitochondrial function. Int J Biol Sci. 2017;13:254-264 pubmed publisher
    Osteogenic differentiation is crucial for the maintenance of bone homeostasis. Sirtuin 3 (SIRT3), a member of sirtuins family, functions as a critical deacetylase that regulates many key proteins...
  9. Osiewacz H. Regulation of the mitochondrial transition pore: impact on mammalian aging. Aging (Albany NY). 2011;3:10-1 pubmed

More Information


  1. Zhang M, Wang S, Cheng Z, Xiong Z, Lv J, Yang Z, et al. Polydatin ameliorates diabetic cardiomyopathy via Sirt3 activation. Biochem Biophys Res Commun. 2017;493:1280-1287 pubmed publisher
    ..Our previous studies have shown that Polydatin (PD) alleviates cardiac dysfunction after myocardial infarction (MI) injury. Nevertheless, the mechanism by which PD regulates diabetic cardiomyopathy has not been reported...
  2. Panza S, Santoro M, De Amicis F, Morelli C, Passarelli V, D Aquila P, et al. Estradiol via estrogen receptor beta influences ROS levels through the transcriptional regulation of SIRT3 in human seminoma TCam-2 cells. Tumour Biol. 2017;39:1010428317701642 pubmed publisher
    ..Future studies may lead to additional strategies for the current therapy of seminoma. ..
  3. Li P, Liu Y, Burns N, Zhao K, Song R. SIRT1 is required for mitochondrial biogenesis reprogramming in hypoxic human pulmonary arteriolar smooth muscle cells. Int J Mol Med. 2017;39:1127-1136 pubmed publisher
    ..Polydatin improves mitochondrial biogenesis and function by enhancing SIRT1 expression in hypoxic human PASMCs. ..
  4. Liu Y, Liu Y, Cheng W, Yin X, Jiang B. The expression of SIRT3 in primary hepatocellular carcinoma and the mechanism of its tumor suppressing effects. Eur Rev Med Pharmacol Sci. 2017;21:978-998 pubmed
    ..SIRT3 can inhibit the growth and proliferation of HepG2 cells and induce HepG2 cell apoptosis. The mechanism may be related to the up-regulation of MnSOD and p53, the up-regulation of Bax and Fas by MnSOD. ..
  5. Liu Y, Zhang D, Chen D. SIRT3: Striking at the heart of aging. Aging (Albany NY). 2011;3:1-2 pubmed
  6. Shin J, Mohrin M, Chen D. Reversing stem cell aging. Oncotarget. 2015;6:14723-4 pubmed
  7. Yu W, Sun Y. Letter to the editor: decreased SIRT3 expression is a good potential biomarker associated with diseases. Am J Physiol Heart Circ Physiol. 2015;308:H258 pubmed publisher
  8. Stram A, Wagner G, Fogler B, Pride P, Hirschey M, Payne R. Progressive mitochondrial protein lysine acetylation and heart failure in a model of Friedreich's ataxia cardiomyopathy. PLoS ONE. 2017;12:e0178354 pubmed publisher
    ..FRDA model hearts have increased mitochondrial protein acetylation and impaired sirtuin 3 (SIRT3) deacetylase activity...
  9. Pacella Ince L, Zander Fox D, Lan M. Mitochondrial SIRT3 and its target glutamate dehydrogenase are altered in follicular cells of women with reduced ovarian reserve or advanced maternal age. Hum Reprod. 2014;29:1490-9 pubmed
    Is the activity of sirtuin 3 (SIRT3) altered in granulosa and cumulus cells from young women with reduced ovarian reserve or women of advanced maternal age? SIRT3 mRNA and active protein in granulosa and cumulus cells were decreased in ..
  10. Traba J, Geiger S, Kwarteng Siaw M, Han K, Ra O, Siegel R, et al. Prolonged fasting suppresses mitochondrial NLRP3 inflammasome assembly and activation via SIRT3-mediated activation of superoxide dismutase 2. J Biol Chem. 2017;292:12153-12164 pubmed publisher
  11. Cheng Y, Dai C, Zhang J. SIRT3-SOD2-ROS pathway is involved in linalool-induced glioma cell apoptotic death. Acta Biochim Pol. 2017;64:343-350 pubmed publisher
    ..In summary, the data demonstrated that linalool exhibited inhibitory effect on glioma cells through regulation of SIRT3-SOD2-ROS signaling. ..
  12. Albani D, Pupillo E, Bianchi E, Chierchia A, Martines R, Forloni G, et al. The role of single-nucleotide variants of the energy metabolism-linked genes SIRT3, PPARGC1A and APOE in amyotrophic lateral sclerosis risk. Genes Genet Syst. 2017;91:301-309 pubmed publisher
    ..The genes selected were sirtuin 3 (SIRT3), peroxisome proliferator-activated receptor-? coactivator-1? (PPARGC1A) and apolipoprotein E (APOE)...
  13. Gounden S, Chuturgoon A. Curcumin Upregulates Antioxidant Defense, Lon Protease, and Heat-Shock Protein 70 Under Hyperglycemic Conditions in Human Hepatoma Cells. J Med Food. 2017;20:465-473 pubmed publisher
    b>Sirtuin 3 (SIRT3) regulates mitochondrial antioxidant (AO) defense and improves mitochondrial disorders. Curcumin protects mitochondria; however, the mechanisms need investigation...
  14. Hsu S, Kass D. Can Nitrite AMPk Up Sirt-ainty to Treat Heart Failure With Preserved Ejection Fraction?. Circulation. 2016;133:692-4 pubmed publisher
  15. Thapa D, Zhang M, Manning J, Guimaraes D, Stoner M, O Doherty R, et al. Acetylation of mitochondrial proteins by GCN5L1 promotes enhanced fatty acid oxidation in the heart. Am J Physiol Heart Circ Physiol. 2017;313:H265-H274 pubmed publisher
    ..Here, we provide new evidence that acetylation of cardiac mitochondrial fatty acid oxidation enzymes by GCN5L1 significantly upregulates their activity in diet-induced obese mice. ..
  16. Zou X, Zhu Y, Park S, Liu G, O Brien J, Jiang H, et al. SIRT3-Mediated Dimerization of IDH2 Directs Cancer Cell Metabolism and Tumor Growth. Cancer Res. 2017;77:3990-3999 pubmed publisher
    ..Overall, these results suggest a potential relationship between SIRT3 enzymatic activity, IDH2-K413 acetylation-determined dimerization, and a cancer-permissive phenotype. Cancer Res; 77(15); 3990-9. ©2017 AACR. ..
  17. Li S, Dou X, Ning H, Song Q, Wei W, Zhang X, et al. Sirtuin 3 acts as a negative regulator of autophagy dictating hepatocyte susceptibility to lipotoxicity. Hepatology. 2017;66:936-952 pubmed publisher
    ..b>Sirtuin 3 (SIRT3) is a nicotinamide adenine dinucleotide-dependent deacetylase located primarily inside mitochondria...
  18. Morigi M, Perico L, Rota C, Longaretti L, Conti S, Rottoli D, et al. Sirtuin 3-dependent mitochondrial dynamic improvements protect against acute kidney injury. J Clin Invest. 2015;125:715-26 pubmed publisher
    ..we determined that both oxidative stress and mitochondrial damage are associated with reduced levels of renal sirtuin 3 (SIRT3)...
  19. Tronchère H, Cinato M, Timotin A, Guitou L, Villedieu C, Thibault H, et al. Inhibition of PIKfyve prevents myocardial apoptosis and hypertrophy through activation of SIRT3 in obese mice. EMBO Mol Med. 2017;9:770-785 pubmed publisher
    ..KO mice. Altogether, these results unravel a novel role for PIKfyve in obesity-associated cardiomyopathy and provide a promising therapeutic strategy to combat cardiometabolic complications in obesity. ..
  20. Ren T, Wang J, Zhu J, Jin M, Wu Y, Guo X, et al. MCU-dependent mitochondrial Ca2+ inhibits NAD+/SIRT3/SOD2 pathway to promote ROS production and metastasis of HCC cells. Oncogene. 2017;36:5897-5909 pubmed publisher
    ..form of nicotinamide adenine dinucleotid (NADH) ratio and the NAD+-dependent deacetylase activity of sirtuin 3 to inhibit superoxide dismutase 2 (SOD2) activity...
  21. Nadtochiy S, Wang Y, Zhang J, Nehrke K, Schafer X, Welle K, et al. Potential mechanisms linking SIRT activity and hypoxic 2-hydroxyglutarate generation: no role for direct enzyme (de)acetylation. Biochem J. 2017;474:2829-2839 pubmed publisher
    ..Overall, these data suggest that a causal relationship should not be assumed between acetylation of metabolic enzymes and their activities, canonical or otherwise. ..
  22. Lombard D, Dash B, Kumar S. Acetyl-ed question in mitochondrial biology?. EMBO J. 2015;34:2597-600 pubmed publisher
  23. Liu L, Nam M, Fan W, Akie T, Hoaglin D, Gao G, et al. Nutrient sensing by the mitochondrial transcription machinery dictates oxidative phosphorylation. J Clin Invest. 2014;124:768-84 pubmed publisher
    b>Sirtuin 3 (SIRT3), an important regulator of energy metabolism and lipid oxidation, is induced in fasted liver mitochondria and implicated in metabolic syndrome...
  24. Dikalova A, Itani H, Nazarewicz R, McMaster W, Flynn C, Uzhachenko R, et al. Sirt3 Impairment and SOD2 Hyperacetylation in Vascular Oxidative Stress and Hypertension. Circ Res. 2017;121:564-574 pubmed publisher
    Clinical studies have shown that Sirt3 (Sirtuin 3) expression declines by 40% by 65 years of age paralleling the increased incidence of hypertension and metabolic conditions further inactivate Sirt3 because of increased NADH (..