Gene Symbol: Sirt3
Description: sirtuin 3
Alias: 2310003L23Rik, AI848213, Sir2l3, NAD-dependent protein deacetylase sirtuin-3, NAD-dependent deacetylase sirtuin-3, SIR2-like protein 3, SIRT3L mitochondrial, mSIR2L3, mitochondrial protein lysine deacetylase, regulatory protein SIR2 homolog 3, silent mating type information regulation 2, (S.cerevisiae, homolog)-like 3
Species: mouse
Products:     Sirt3

Top Publications

  1. 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...
  2. Koyama T, Kume S, Koya D, Araki S, Isshiki K, Chin Kanasaki M, et al. SIRT3 attenuates palmitate-induced ROS production and inflammation in proximal tubular cells. Free Radic Biol Med. 2011;51:1258-67 pubmed publisher
    ..b>SIRT3 is an antiaging molecule regulated by calorie restriction and mitochondria-localized NAD(+)-dependent deacetylase...
  3. Finley L, Carracedo A, Lee J, Souza A, Egia A, Zhang J, et al. SIRT3 opposes reprogramming of cancer cell metabolism through HIF1? destabilization. Cancer Cell. 2011;19:416-28 pubmed publisher
    ..Here, we show that the mitochondrial NAD-dependent deacetylase SIRT3 is a crucial regulator of the Warburg effect...
  4. Bao J, Lu Z, Joseph J, Carabenciov D, Dimond C, Pang L, et al. Characterization of the murine SIRT3 mitochondrial localization sequence and comparison of mitochondrial enrichment and deacetylase activity of long and short SIRT3 isoforms. J Cell Biochem. 2010;110:238-47 pubmed publisher
    b>SIRT3 is identified as the major mitochondrial deacetylase...
  5. Li L, Zeng H, Hou X, He X, Chen J. Myocardial injection of apelin-overexpressing bone marrow cells improves cardiac repair via upregulation of Sirt3 after myocardial infarction. PLoS ONE. 2013;8:e71041 pubmed publisher
    ..Mechanistically, Apelin-BMCs treatment led to a significant increase in Sirtuin3 (Sirt3) expression and reduction of reactive oxygen species (ROS) formation...
  6. Finley L, Haas W, Desquiret Dumas V, Wallace D, Procaccio V, Gygi S, et al. Succinate dehydrogenase is a direct target of sirtuin 3 deacetylase activity. PLoS ONE. 2011;6:e23295 pubmed publisher
    ..b>SIRT3 is localized to mitochondria, where it deacetylates and activates a number of enzymes involved in fuel oxidation ..
  7. 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 ..
  8. Hirschey M, Shimazu T, Goetzman E, Jing E, Schwer B, Lombard D, et al. SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature. 2010;464:121-5 pubmed publisher
    ..Sirtuin 3 (SIRT3) is localized in the mitochondrial matrix, where it regulates the acetylation levels of metabolic enzymes, ..
  9. Kim S, Lu H, Alano C. Neuronal Sirt3 protects against excitotoxic injury in mouse cortical neuron culture. PLoS ONE. 2011;6:e14731 pubmed publisher
    ..Among the known Sirt isoforms (Sirt1-7), Sirt3 was identified as a stress responsive deacetylase recently shown to play a role in protecting cells under stress ..

More Information


  1. Cooper H, Huang J, Verdin E, Spelbrink J. A new splice variant of the mouse SIRT3 gene encodes the mitochondrial precursor protein. PLoS ONE. 2009;4:e4986 pubmed publisher
    ..Three mammalian sirtuins, SIRT3-5 are mitochondrial...
  2. Hafner A, Dai J, Gomes A, Xiao C, Palmeira C, Rosenzweig A, et al. Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy. Aging (Albany NY). 2010;2:914-23 pubmed
    ..Here we report that the NAD+-dependent deacetylase SIRT3 deacetylates the regulatory component of the mPTP, cyclophilin D (CypD) on lysine 166, adjacent to the binding ..
  3. Hallows W, Yu W, Smith B, Devries M, Devires M, Ellinger J, et al. Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction. Mol Cell. 2011;41:139-49 pubmed publisher
    ..Here we utilize acetyl-peptide arrays and metabolomic analyses to identify substrates of mitochondrial deacetylase Sirt3. We identified ornithine transcarbamoylase (OTC) from the urea cycle, and enzymes involved in β-oxidation...
  4. Palacios O, Carmona J, Michan S, Chen K, Manabe Y, Ward J, et al. Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1alpha in skeletal muscle. Aging (Albany NY). 2009;1:771-83 pubmed
    b>SIRT3 is a member of the sirtuin family of NAD(+)-dependent deacetylases, which is localized to the mitochondria and is enriched in kidney, brown adipose tissue, heart, and other metabolically active tissues...
  5. Bharathi S, Zhang Y, Mohsen A, Uppala R, Balasubramani M, Schreiber E, et al. Sirtuin 3 (SIRT3) protein regulates long-chain acyl-CoA dehydrogenase by deacetylating conserved lysines near the active site. J Biol Chem. 2013;288:33837-47 pubmed publisher
    ..We previously demonstrated increased LCAD lysine acetylation in SIRT3 knockout mice concomitant with reduced LCAD activity and reduced fatty acid oxidation...
  6. Shimazu T, Hirschey M, Hua L, Dittenhafer Reed K, Schwer B, Lombard D, et al. SIRT3 deacetylates mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 and regulates ketone body production. Cell Metab. 2010;12:654-61 pubmed publisher
    The mitochondrial sirtuin SIRT3 regulates metabolic homeostasis during fasting and calorie restriction...
  7. Jing E, Emanuelli B, Hirschey M, Boucher J, Lee K, Lombard D, et al. Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production. Proc Natl Acad Sci U S A. 2011;108:14608-13 pubmed publisher
    b>Sirt3 is a member of the sirtuin family of protein deacetylases that is localized in mitochondria and regulates mitochondrial function...
  8. 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)...
  9. Hirschey M, Shimazu T, Jing E, Grueter C, Collins A, Aouizerat B, et al. SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome. Mol Cell. 2011;44:177-90 pubmed publisher
    ..mitochondrial protein hyperacetylation in mice and downregulation of the major mitochondrial protein deacetylase SIRT3. Mice lacking SIRT3 (SIRT3KO) placed on a HFD show accelerated obesity, insulin resistance, hyperlipidemia, and ..
  10. Kawamura Y, Uchijima Y, Horike N, Tonami K, Nishiyama K, Amano T, et al. Sirt3 protects in vitro-fertilized mouse preimplantation embryos against oxidative stress-induced p53-mediated developmental arrest. J Clin Invest. 2010;120:2817-28 pubmed publisher
    ..These effects were recapitulated by siRNA-induced knockdown of Sirt3, which is involved in mitochondrial energy metabolism, and in Sirt3-/- embryos...
  11. Pillai V, Sundaresan N, Kim G, Gupta M, Rajamohan S, Pillai J, et al. Exogenous NAD blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMP-activated kinase pathway. J Biol Chem. 2010;285:3133-44 pubmed publisher
    ..By using gene knock-out and transgenic mouse models of SIRT3 and SIRT1, we showed that the anti-hypertrophic effects of exogenous NAD are mediated through activation of SIRT3, ..
  12. Kong X, Wang R, Xue Y, Liu X, Zhang H, Chen Y, et al. Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis. PLoS ONE. 2010;5:e11707 pubmed publisher
    Sirtuin 3 (SIRT3) is one of the seven mammalian sirtuins, which are homologs of the yeast Sir2 gene. SIRT3 is the only sirtuin with a reported association with the human life span...
  13. Hebert A, Dittenhafer Reed K, Yu W, Bailey D, Selen E, Boersma M, et al. Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome. Mol Cell. 2013;49:186-99 pubmed publisher
    ..acetyl-proteome during CR versus control diet in mice that were wild-type or lacked the protein deacetylase SIRT3. Quantification of 3,285 acetylation sites-2,193 from mitochondrial proteins-rendered a comprehensive atlas of the ..
  14. Brown K, Xie S, Qiu X, Mohrin M, Shin J, Liu Y, et al. SIRT3 reverses aging-associated degeneration. Cell Rep. 2013;3:319-27 pubmed publisher
    ..We show that SIRT3, a mammalian sirtuin that regulates the global acetylation landscape of mitochondrial proteins and reduces ..
  15. Kendrick A, Choudhury M, Rahman S, McCurdy C, Friederich M, Van Hove J, et al. Fatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylation. Biochem J. 2011;433:505-14 pubmed publisher
    ..Livers of mice fed on the HFD had reduced SIRT3 activity, a 3-fold decrease in hepatic NAD(+) levels and increased mitochondrial protein oxidation...
  16. Sundaresan N, Gupta M, Kim G, Rajamohan S, Isbatan A, Gupta M. Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. J Clin Invest. 2009;119:2758-71 pubmed publisher
    Sirtuin 3 (SIRT3) is a member of the sirtuin family of proteins that promote longevity in many organisms. Increased expression of SIRT3 has been linked to an extended life span in humans...
  17. Qiu X, Brown K, Hirschey M, Verdin E, Chen D. Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab. 2010;12:662-7 pubmed publisher
    ..Here, we show that the protective effects of CR on oxidative stress and damage are diminished in mice lacking SIRT3, a mitochondrial deacetylase...
  18. Yu W, Dittenhafer Reed K, Denu J. SIRT3 protein deacetylates isocitrate dehydrogenase 2 (IDH2) and regulates mitochondrial redox status. J Biol Chem. 2012;287:14078-86 pubmed publisher
    ..Previously, we demonstrated that the NAD(+)-dependent deacetylase SIRT3 was essential for the prevention of age-related hearing loss in mice fed a calorically restricted diet...
  19. Fritz K, Galligan J, Smathers R, ROEDE J, Shearn C, Reigan P, et al. 4-Hydroxynonenal inhibits SIRT3 via thiol-specific modification. Chem Res Toxicol. 2011;24:651-62 pubmed publisher
    ..In the present study, a greater than 2-fold increase in protein carbonylation of sirtuin 3 (SIRT3), a mitochondrial class III histone deacetylase, is reported in liver mitochondrial extracts of ethanol-consuming ..
  20. He J, Hu B, Shi X, Weidert E, Lu P, Xu M, et al. Activation of the aryl hydrocarbon receptor sensitizes mice to nonalcoholic steatohepatitis by deactivating mitochondrial sirtuin deacetylase Sirt3. Mol Cell Biol. 2013;33:2047-55 pubmed publisher
    ..polymerase (TiPARP) gene expression, depleted NAD(+), deactivated the mitochondrial sirtuin deacetylase 3 (Sirt3), increased SOD2 acetylation, and thereby decreased SOD2 activity...
  21. Kim H, Patel K, Muldoon Jacobs K, Bisht K, Aykin Burns N, Pennington J, et al. SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell. 2010;17:41-52 pubmed publisher
    ..This work demonstrates that SIRT3(-/-) mouse embryonic fibroblasts (MEFs) exhibit abnormal mitochondrial physiology as well as increases in stress-..
  22. Sundaresan N, Samant S, Pillai V, Rajamohan S, Gupta M. SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku70. Mol Cell Biol. 2008;28:6384-401 pubmed publisher
    ..Among them, SIRT3 is the only sirtuin whose increased expression has been shown to correlate with an extended life span in humans...
  23. Hallows W, Albaugh B, Denu J. Where in the cell is SIRT3?--functional localization of an NAD+-dependent protein deacetylase. Biochem J. 2008;411:e11-3 pubmed publisher
    ..b>SIRT3 (sirtuin 3), a human homologue of Sir2 (silent information regulator 2), has been genetically linked to lifespan ..
  24. Shi T, Wang F, Stieren E, Tong Q. SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. J Biol Chem. 2005;280:13560-7 pubmed
    b>SIRT3 is one of the seven mammalian sirtuin homologs of the yeast Sir2 gene, which mediates the effect of caloric restriction on life span extension in yeast and Caenorhabditis elegans...
  25. Giralt A, Hondares E, Villena J, Ribas F, Diaz Delfin J, Giralt M, et al. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha controls transcription of the Sirt3 gene, an essential component of the thermogenic brown adipocyte phenotype. J Biol Chem. 2011;286:16958-66 pubmed publisher
    b>Sirt3 (silent mating type information regulation 2, homolog 3), a member of the sirtuin family of protein deacetylases with multiple actions on metabolism and gene expression is expressed in association with brown adipocyte ..
  26. 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
    ..Our results revealed that the two mouse Sir2-like proteins (mSIR2L2 and mSIR2L3) are most similar to the human Sir2-like proteins SIR2L2 and SIR2L3, respectively...
  27. 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 ..
  28. Someya S, Yu W, Hallows W, Xu J, Vann J, Leeuwenburgh C, et al. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell. 2010;143:802-12 pubmed publisher
    ..prevents AHL in wild-type mice but fails to modify these phenotypes in mice lacking the mitochondrial deacetylase Sirt3, a member of the sirtuin family...
  29. Yang Y, Hubbard B, Sinclair D, Tong Q. Characterization of murine SIRT3 transcript variants and corresponding protein products. J Cell Biochem. 2010;111:1051-8 pubmed publisher
    b>SIRT3 is one of the seven mammalian sirtuin homologs of the yeast SIR2 gene. SIRT3 possesses NAD(+)-dependent protein deacetylase activity...
  30. Fernandez Marcos P, Jeninga E, Canto C, Harach T, de Boer V, Andreux P, et al. Muscle or liver-specific Sirt3 deficiency induces hyperacetylation of mitochondrial proteins without affecting global metabolic homeostasis. Sci Rep. 2012;2:425 pubmed publisher
    b>Sirt3 is a mitochondrial sirtuin, predominantly expressed in highly metabolic tissues...
  31. Yang Y, Chen K, Tong Q. Murine Sirt3 protein isoforms have variable half-lives. Gene. 2011;488:46-51 pubmed publisher
    b>Sirt3 is a NAD+-dependent protein deacetylase mainly localized in mitochondria...
  32. 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...
  33. Cimen H, Han M, Yang Y, Tong Q, Koc H, Koc E. Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondria. Biochemistry. 2010;49:304-11 pubmed publisher
    A member of the sirtuin family of NAD(+)-dependent deacetylases, SIRT3, is identified as one of the major mitochondrial deacetylases located in mammalian mitochondria responsible for deacetylation of several metabolic enzymes and ..
  34. Nakagawa T, Lomb D, Haigis M, Guarente L. SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell. 2009;137:560-70 pubmed publisher
    ..Similar effects occur during long-term calorie restriction or a high protein diet. These findings demonstrate SIRT5 plays a pivotal role in ammonia detoxification and disposal by activating CPS1. ..
  35. Tao R, Coleman M, Pennington J, Ozden O, Park S, Jiang H, et al. Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress. Mol Cell. 2010;40:893-904 pubmed publisher
    Genetic deletion of the mitochondrial deacetylase sirtuin-3 (Sirt3) results in increased mitochondrial superoxide, a tumor-permissive environment, and mammary tumor development...
  36. Ahn B, Kim H, Song S, Lee I, Liu J, Vassilopoulos A, et al. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci U S A. 2008;105:14447-52 pubmed publisher
    Here, we demonstrate a role for the mitochondrial NAD-dependent deacetylase Sirt3 in the maintenance of basal ATP levels and as a regulator of mitochondrial electron transport...
  37. Dittenhafer Reed K, Richards A, Fan J, Smallegan M, Fotuhi Siahpirani A, Kemmerer Z, et al. SIRT3 mediates multi-tissue coupling for metabolic fuel switching. Cell Metab. 2015;21:637-46 pubmed publisher
    b>SIRT3 is a member of the Sirtuin family of NAD(+)-dependent deacylases and plays a critical role in metabolic regulation...
  38. Duan W, Li Y, Liu F, Deng J, Wu Y, Yuan W, et al. A SIRT3/AMPK/autophagy network orchestrates the protective effects of trans-resveratrol in stressed peritoneal macrophages and RAW 264.7 macrophages. Free Radic Biol Med. 2016;95:230-42 pubmed publisher
    ..Resveratrol promoted autophagy via upregulating SIRT3 expression and phosphorylation of AMP-activated protein kinase (AMPK)...
  39. Brown K, Maqsood S, Huang J, Pan Y, Harkcom W, Li W, et al. Activation of SIRT3 by the NAD⁺ precursor nicotinamide riboside protects from noise-induced hearing loss. Cell Metab. 2014;20:1059-68 pubmed publisher
    ..These effects are mediated by the NAD(+)-dependent mitochondrial sirtuin, SIRT3, since SIRT3-overexpressing mice are resistant to NIHL and SIRT3 deletion abrogates the protective effects of NR ..
  40. Sheng S, Kang Y, Guo Y, Pu Q, Cai M, Tu Z. Overexpression of Sirt3 inhibits lipid accumulation in macrophages through mitochondrial IDH2 deacetylation. Int J Clin Exp Pathol. 2015;8:9196-201 pubmed
    This study aims to explore the relationship between Sirt3 expression and lipid accumulation in macrophages by inducing mitochondrial IDH2 deacetylation...
  41. Fukasawa K, Li W, Yagi K, Luo C, Li S. Molecular evolution of mammalian lactate dehydrogenase-A genes and pseudogenes: association of a mouse processed pseudogene with a B1 repetitive sequence. Mol Biol Evol. 1986;3:330-42 pubmed
    ..20 X 10(-9), which is considerably lower than the average rate of 0.88 X 10(-9) for 35 mammalian genes. Thus, the mammalian LDH-A gene appears to be highly conserved in evolution. ..
  42. Barger J, Anderson R, Newton M, da Silva C, Vann J, Pugh T, et al. A conserved transcriptional signature of delayed aging and reduced disease vulnerability is partially mediated by SIRT3. PLoS ONE. 2015;10:e0120738 pubmed publisher
    ..Mice lacking the NAD-dependent deacetylase SIRT3 fail to induce mitochondrial and anti-inflammatory elements of the signature in response to CR, suggesting a ..
  43. Cui Y, Qin L, Wu J, Qu X, Hou C, Sun W, et al. SIRT3 Enhances Glycolysis and Proliferation in SIRT3-Expressing Gastric Cancer Cells. PLoS ONE. 2015;10:e0129834 pubmed publisher
    b>SIRT3 is a key NAD+-dependent protein deacetylase in the mitochondria of mammalian cells, functioning to prevent cell aging and transformation via regulation of mitochondrial metabolic homeostasis...
  44. Winnik S, Gaul D, Preitner F, Lohmann C, Weber J, Miranda M, et al. Deletion of Sirt3 does not affect atherosclerosis but accelerates weight gain and impairs rapid metabolic adaptation in LDL receptor knockout mice: implications for cardiovascular risk factor development. Basic Res Cardiol. 2014;109:399 pubmed publisher
    b>Sirt3 is a mitochondrial NAD(+)-dependent deacetylase that governs mitochondrial metabolism and reactive oxygen species homeostasis. Sirt3 deficiency has been reported to accelerate the development of the metabolic syndrome...
  45. Novgorodov S, Riley C, Keffler J, Yu J, Kindy M, Macklin W, et al. SIRT3 Deacetylates Ceramide Synthases: IMPLICATIONS FOR MITOCHONDRIAL DYSFUNCTION AND BRAIN INJURY. J Biol Chem. 2016;291:1957-73 pubmed publisher
    ..Herein, we report that SIRT3 regulates mitochondrial ceramide biosynthesis via deacetylation of ceramide synthase (CerS) 1, 2, and 6...
  46. Parr C, Mirzaei N, Christian M, Sastre M. Activation of the Wnt/β-catenin pathway represses the transcription of the β-amyloid precursor protein cleaving enzyme (BACE1) via binding of T-cell factor-4 to BACE1 promoter. FASEB J. 2015;29:623-35 pubmed publisher
    ..Parr, C., Mirzaei, N., Christian, M., and Sastre, M. Activation of the Wnt/β-catenin pathway represses the transcription of the β-amyloid precursor protein cleaving enzyme (BACE1) via binding of T-cell factor-4 to BACE1 promoter. ..
  47. Bugger H, Witt C, Bode C. Mitochondrial sirtuins in the heart. Heart Fail Rev. 2016;21:519-28 pubmed publisher
    ..In mammals, seven sirtuins have been identified, SIRT1-7. SIRT3-5 are mainly or exclusively localized within mitochondria and mainly participate in the regulation of energy ..
  48. Yang W, Nagasawa K, Münch C, Xu Y, Satterstrom K, Jeong S, et al. Mitochondrial Sirtuin Network Reveals Dynamic SIRT3-Dependent Deacetylation in Response to Membrane Depolarization. Cell. 2016;167:985-1000.e21 pubmed publisher
    Mitochondrial sirtuins, SIRT3-5, are NAD+-dependent deacylases and ADP-ribosyltransferases that are critical for stress responses...
  49. Lu Z, Bourdi M, Li J, Aponte A, Chen Y, Lombard D, et al. SIRT3-dependent deacetylation exacerbates acetaminophen hepatotoxicity. EMBO Rep. 2011;12:840-6 pubmed publisher
    ..As fasting promotes SIRT3-mediated mitochondrial-protein deacetylation and acetaminophen metabolites bind to lysine residues, we ..
  50. Li N, Zhang J, Yan X, Zhang C, Liu H, Shan X, et al. SIRT3-KLF15 signaling ameliorates kidney injury induced by hypertension. Oncotarget. 2017;8:39592-39604 pubmed publisher
    Renal fibrosis participates in the progression of hypertension-induced kidney injury. The effect of SIRT3, a member of the NAD+-dependent deacetylase family, in hypertensive nephropathy remains unclear...
  51. Wagner G, Pride P, Babbey C, Payne R. Friedreich's ataxia reveals a mechanism for coordinate regulation of oxidative metabolism via feedback inhibition of the SIRT3 deacetylase. Hum Mol Genet. 2012;21:2688-97 pubmed publisher
    ..phenotype develops concurrently with cardiac hypertrophy and is caused by inhibition of the NAD(+)-dependent SIRT3 deacetylase...
  52. 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
    ..that both oxidative stress and mitochondrial damage are associated with reduced levels of renal sirtuin 3 (SIRT3)...
  53. Chen T, Liu J, Li N, Wang S, Liu H, Li J, et al. Mouse SIRT3 attenuates hypertrophy-related lipid accumulation in the heart through the deacetylation of LCAD. PLoS ONE. 2015;10:e0118909 pubmed publisher
    ..b>SIRT3, a mitochondrial NAD+-dependent deacetylase, has been demonstrated to play a crucial role in controlling the ..
  54. Martin J, Balmer M, Rajendran S, Maurhofer O, Dufour J, St Pierre M. Nutritional stress exacerbates hepatic steatosis induced by deletion of the histidine nucleotide-binding (Hint2) mitochondrial protein. Am J Physiol Gastrointest Liver Physiol. 2016;310:G497-509 pubmed publisher
    ..The absence of Hint2 deregulates the posttranslational modification of several mitochondrial proteins, which impedes the adaptation to episodes of nutritional stress. ..
  55. Liu L, Peritore C, Ginsberg J, Kayhan M, Donmez G. SIRT3 attenuates MPTP-induced nigrostriatal degeneration via enhancing mitochondrial antioxidant capacity. Neurochem Res. 2015;40:600-8 pubmed publisher
    ..Sirtuin3 (SIRT3) is the major mitochondria NAD(+)-dependent deacetylase that acts as a regulator of mitochondrial protein function;..
  56. Lantier L, Williams A, Williams I, Yang K, Bracy D, Goelzer M, et al. SIRT3 Is Crucial for Maintaining Skeletal Muscle Insulin Action and Protects Against Severe Insulin Resistance in High-Fat-Fed Mice. Diabetes. 2015;64:3081-92 pubmed publisher
    ..Sirtuin 3 (SIRT3), the primary mitochondrial deacetylase, has been linked to energy homeostasis...
  57. Witt O, Deubzer H, Milde T, Oehme I. HDAC family: What are the cancer relevant targets?. Cancer Lett. 2009;277:8-21 pubmed publisher
    ..The aim of this review is to discuss individual HDAC family members as drug targets in cancer taking into consideration their function under physiological conditions and their oncogenic potential in malignant disease. ..
  58. Zhang Y, Bharathi S, Rardin M, Uppala R, Verdin E, Gibson B, et al. SIRT3 and SIRT5 regulate the enzyme activity and cardiolipin binding of very long-chain acyl-CoA dehydrogenase. PLoS ONE. 2015;10:e0122297 pubmed publisher
    b>SIRT3 and SIRT5 have been shown to regulate mitochondrial fatty acid oxidation but the molecular mechanisms behind the regulation are lacking...
  59. 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 (..
  60. Alrob O, Sankaralingam S, Ma C, Wagg C, Fillmore N, Jaswal J, et al. Obesity-induced lysine acetylation increases cardiac fatty acid oxidation and impairs insulin signalling. Cardiovasc Res. 2014;103:485-97 pubmed publisher
    ..whether lysine acetylation controls heart glucose and fatty acid oxidation in high-fat diet (HFD) obese and SIRT3 knockout (KO) mice...
  61. Bruce K, Szczepankiewicz D, Sihota K, Ravindraanandan M, Thomas H, Lillycrop K, et al. Altered cellular redox status, sirtuin abundance and clock gene expression in a mouse model of developmentally primed NASH. Biochim Biophys Acta. 2016;1861:584-93 pubmed publisher
    ..NAFLD progression, cellular redox status, sirtuin expression (Sirt1, Sirt3), and the expression of core clock genes (Clock, Bmal1, Per2, Cry2) and clock-controlled genes involved in lipid ..
  62. Zhang M, Lin J, Wang S, Cheng Z, Hu J, Wang T, et al. Melatonin protects against diabetic cardiomyopathy through Mst1/Sirt3 signaling. J Pineal Res. 2017;63: pubmed publisher
    ..Furthermore, melatonin inhibited Mst1 phosphorylation and promoted Sirt3 expression in DCM. These results indicated that melatonin may exert its effects through Mst1/Sirt3 signaling...
  63. Xu H, Hertzel A, Steen K, Bernlohr D. Loss of Fatty Acid Binding Protein 4/aP2 Reduces Macrophage Inflammation Through Activation of SIRT3. Mol Endocrinol. 2016;30:325-34 pubmed publisher
    ..Here, we show that loss of FABP4/aP2 in macrophages additionally induces sirtuin 3 (SIRT3) expression and that monounsaturated fatty acids (C16:1, C18:1) lead to increased SIRT3 protein expression...
  64. 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...
  65. Koentges C, Pfeil K, Schnick T, Wiese S, Dahlbock R, Cimolai M, et al. SIRT3 deficiency impairs mitochondrial and contractile function in the heart. Basic Res Cardiol. 2015;110:36 pubmed publisher
    Sirtuin 3 (SIRT3) is a mitochondrial NAD(+)-dependent deacetylase that regulates energy metabolic enzymes by reversible protein lysine acetylation in various extracardiac tissues...
  66. Fritz K, Green M, Petersen D, Hirschey M. Ethanol metabolism modifies hepatic protein acylation in mice. PLoS ONE. 2013;8:e75868 pubmed publisher
    ..The mitochondrial deacetylase SIRT3 regulates the acetylation status of several mitochondrial proteins, including those involved in ethanol metabolism...
  67. Liang Q, Benavides G, Vassilopoulos A, Gius D, Darley Usmar V, Zhang J. Bioenergetic and autophagic control by Sirt3 in response to nutrient deprivation in mouse embryonic fibroblasts. Biochem J. 2013;454:249-57 pubmed publisher
    b>Sirt3 (sirtuin 3) is an NAD-dependent deacetylase localized to mitochondria...