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| Sirt3SummaryGene Symbol: Sirt3 Description: sirtuin 3 (silent mating type information regulation 2, homolog) 3 (S. cerevisiae) Alias: 2310003L23Rik, AI848213, Sir2l3, NAD-dependent deacetylase sirtuin-3, NAD-dependent protein 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 Top Publications
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Publications
SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stressHyun Seok Kim
Genetics of Development and Disease Branch, NIDDK, NIH, Bethesda, MD 20892, USA
Cancer Cell 17:41-52. 2010..This work demonstrates that SIRT3(-/-) mouse embryonic fibroblasts (MEFs) exhibit abnormal mitochondrial physiology as well as increases in stress-..
SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylationMatthew D Hirschey
Gladstone Institute of Virology and Immunology, San Francisco, California 94158, USA
Nature 464:121-5. 2010..Sirtuin 3 (SIRT3) is localized in the mitochondrial matrix, where it regulates the acetylation levels of metabolic enzymes, ..- A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasisBong Hyun Ahn
Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 105:14447-52. 2008Here, 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... - Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in miceNagalingam R Sundaresan
Department of Surgery, University of Chicago, Chicago, Illinois 60637, USA
J Clin Invest 119:2758-71. 2009Sirtuin 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... - Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylationDavid B Lombard
Howard Hughes Medical Institute, The Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
Mol Cell Biol 27:8807-14. 2007..Studies of the sirtuin SIRT3 have so far been limited to cell culture systems... - SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycleTakashi Nakagawa
Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139, USA
Cell 137:560-70. 2009..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... 
SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytesTong Shi
United States Department of Agriculture Agricultural Research Service Children s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA
J Biol Chem 280:13560-7. 2005b>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...- SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku70Nagalingam R Sundaresan
University of Chicago Medical Center, Committee on Cellular and Molecular Physiology, Biological Science Division, University of Chicago, Chicago, Illinois 60637, USA
Mol Cell Biol 28:6384-401. 2008..Among them, SIRT3 is the only sirtuin whose increased expression has been shown to correlate with an extended life span in humans... - Localization of mouse mitochondrial SIRT proteins: shift of SIRT3 to nucleus by co-expression with SIRT5Yasuhiko Nakamura
Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, 54 Kawahara cho, Shogoin, Sakyo ku, Kyoto 606 8507, Japan
Biochem Biophys Res Commun 366:174-9. 2008Yeast 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... - SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilizationLydia W S Finley
Department of Pathology, The Paul F Glenn Labs for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA 02115, USA
Cancer Cell 19:416-28. 2011..Here, we show that the mitochondrial NAD-dependent deacetylase SIRT3 is a crucial regulator of the Warburg effect... - SIRT3 deacetylates mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 and regulates ketone body productionTadahiro Shimazu
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA
Cell Metab 12:654-61. 2010The mitochondrial sirtuin SIRT3 regulates metabolic homeostasis during fasting and calorie restriction... - Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restrictionWilliam C Hallows
Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53706, USA
Mol Cell 41:139-49. 2011..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... - Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1alpha in skeletal muscleOrsolya M Palacios
USDA ARS Children s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
Aging (Albany NY) 1:771-83. 2009b>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... - Peroxisome proliferator-activated receptor-gamma coactivator-1alpha controls transcription of the Sirt3 gene, an essential component of the thermogenic brown adipocyte phenotypeAlbert Giralt
Departament de Bioquimica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, and CIBER Fisiopatologia de la Obesidad y Nutricion, 08028 Barcelona, Spain
J Biol Chem 286:16958-66. 2011b>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 .. - Where in the cell is SIRT3?--functional localization of an NAD+-dependent protein deacetylaseWilliam C Hallows
Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706, USA
Biochem J 411:e11-3. 2008..b>SIRT3 (sirtuin 3), a human homologue of Sir2 (silent information regulator 2), has been genetically linked to lifespan .. - Characterization of murine SIRT3 transcript variants and corresponding protein productsYongjie Yang
USDA ARS Children s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA
J Cell Biochem 111:1051-8. 2010b>SIRT3 is one of the seven mammalian sirtuin homologs of the yeast SIR2 gene. SIRT3 possesses NAD(+)-dependent protein deacetylase activity... - A new splice variant of the mouse SIRT3 gene encodes the mitochondrial precursor proteinHelen M Cooper
University of Tampere, Institute of Medical Technology and Tampere University Hospital, Tampere, Finland
PLoS ONE 4:e4986. 2009..Three mammalian sirtuins, SIRT3-5 are mitochondrial... - Biochemical characterization, localization, and tissue distribution of the longer form of mouse SIRT3Lei Jin
Sirtris, a GSK Company, 200 Technology Square, Cambridge, MA 02139, USA
Protein Sci 18:514-25. 2009b>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 .. - Cloning and characterization of two mouse genes with homology to the yeast Sir2 geneY H Yang
Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut, 06536, USA
Genomics 69:355-69. 2000..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... - Neuronal Sirt3 protects against excitotoxic injury in mouse cortical neuron cultureSun Hee Kim
Department of Neurology, Veterans Affairs Medical Center, San Francisco, California, United States of America
PLoS ONE 6:e14731. 2011..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 .. - Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophyAngela V Hafner
Harvard Medical School, Department of Pathology and Glenn Labs for Aging Research, Boston, MA 02115, USA
Aging (Albany NY) 2:914-23. 2010..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 .. - 4-Hydroxynonenal inhibits SIRT3 via thiol-specific modificationKristofer S Fritz
Department of Pharmaceutical Sciences, Graduate Program in Toxicology, School of Pharmacy, University of Colorado Denver, Aurora, USA
Chem Res Toxicol 24:651-62. 2011..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 .. - SIRT3 attenuates palmitate-induced ROS production and inflammation in proximal tubular cellsTetsuro Koyama
Department of Medicine, Shiga University of Medical Science, Otsu, Shiga 520 2192, Japan
Free Radic Biol Med 51:1258-67. 2011..b>SIRT3 is an antiaging molecule regulated by calorie restriction and mitochondria-localized NAD(+)-dependent deacetylase... - SIRT3-dependent deacetylation exacerbates acetaminophen hepatotoxicityZhongping Lu
Center for Molecular Medicine, NHLBI, National Institutes of Health, Building 10 CRC, Room 5 3150, 10 Center Drive, Bethesda, Maryland 20892, USA
EMBO Rep 12:840-6. 2011..As fasting promotes SIRT3-mediated mitochondrial-protein deacetylation and acetaminophen metabolites bind to lysine residues, we .. - Murine Sirt3 protein isoforms have variable half-livesYongjie Yang
Children s Nutrition Research Center, Baylor College of Medicine, 1100 Bates Street, Houston, TX 77030, USA
Gene 488:46-51. 2011b>Sirt3 is a NAD+-dependent protein deacetylase mainly localized in mitochondria... - SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndromeMatthew D Hirschey
Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA
Mol Cell 44:177-90. 2011..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 .. - Succinate dehydrogenase is a direct target of sirtuin 3 deacetylase activityLydia W S Finley
Department of Pathology, The Paul F Glenn Labs for the Biological Mechanisms of Aging, Harvard Medical School, Boston, Massachusetts, United States of America
PLoS ONE 6:e23295. 2011..b>SIRT3 is localized to mitochondria, where it deacetylates and activates a number of enzymes involved in fuel oxidation .. - Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species productionEnxuan Jing
Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
Proc Natl Acad Sci U S A 108:14608-13. 2011b>Sirt3 is a member of the sirtuin family of protein deacetylases that is localized in mitochondria and regulates mitochondrial function... - Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stressRanda Tao
Howard Hughes Medical Institute and Molecular Radiation Oncology, Radiation Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA
Mol Cell 40:893-904. 2010Genetic deletion of the mitochondrial deacetylase sirtuin-3 (Sirt3) results in increased mitochondrial superoxide, a tumor-permissive environment, and mammary tumor development... - Genomic organization and localization of the NAD-dependent histone deacetylase gene sirtuin 3 (Sirt3) in the mouseUlrich Mahlknecht
Saarland University Medical Center, Department of Internal Medicine, Homburg Saar, Germany
Int J Oncol 38:813-22. 2011Sirtuin 3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, which belongs to the Silent information regulator 2 (Sir2) family of histone deacetylases (sirtuin HDACs)... - HDAC family: What are the cancer relevant targets?Olaf Witt
CCU Pediatric Oncology G340, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, Germany
Cancer Lett 277:8-21. 2009..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... - Molecular evolution of mammalian lactate dehydrogenase-A genes and pseudogenes: association of a mouse processed pseudogene with a B1 repetitive sequenceK M Fukasawa
Laboratory of Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
Mol Biol Evol 3:330-42. 1986..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... - Exogenous NAD blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMP-activated kinase pathwayVinodkumar B Pillai
Department of Surgery, University of Chicago, Chicago, Illinois 60637, USA
J Biol Chem 285:3133-44. 2010..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, .. - Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondriaHuseyin Cimen
Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA
Biochemistry 49:304-11. 2010A 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 .. - Characterization of the murine SIRT3 mitochondrial localization sequence and comparison of mitochondrial enrichment and deacetylase activity of long and short SIRT3 isoformsJianjun Bao
Translational Medicine Branch, NHLBI, NIH, Bethesda, Maryland, USA
J Cell Biochem 110:238-47. 2010b>SIRT3 is identified as the major mitochondrial deacetylase... - Sirt3 protects in vitro-fertilized mouse preimplantation embryos against oxidative stress-induced p53-mediated developmental arrestYumiko Kawamura
Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
J Clin Invest 120:2817-28. 2010..These effects were recapitulated by siRNA-induced knockdown of Sirt3, which is involved in mitochondrial energy metabolism, and in Sirt3-/- embryos... - Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesisXingxing Kong
The National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
PLoS ONE 5:e11707. 2010Sirtuin 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... - Fatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylationAgnieszka A Kendrick
Nutrition and Obesity Research Center, Department of Anesthesiology, University of Colorado School of Medicine, Aurora, 80045, USA
Biochem J 433:505-14. 2011..Livers of mice fed on the HFD had reduced SIRT3 activity, a 3-fold decrease in hepatic NAD(+) levels and increased mitochondrial protein oxidation... - Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restrictionShinichi Someya
Departments of Genetics and Medical Genetics, University of Wisconsin, Madison, 53706, USA
Cell 143:802-12. 2010..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... - NAD+-dependent deacetylase SIRT3 regulates mitochondrial protein synthesis by deacetylation of the ribosomal protein MRPL10Yongjie Yang
Children s Nutrition Research Center, Baylor College of Medicine, Houston, Texas 77030, USA
J Biol Chem 285:7417-29. 2010A member of the sirtuin family of NAD(+)-dependent deacetylases, SIRT3, is located in mammalian mitochondria and is important for regulation of mitochondrial metabolism, cell survival, and longevity... - Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activationXiaolei Qiu
Department of Nutritional Science and Toxicology, University of California, Berkeley, CA 94720, USA
Cell Metab 12:662-7. 2010..Here, we show that the protective effects of CR on oxidative stress and damage are diminished in mice lacking SIRT3, a mitochondrial deacetylase... - New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditureYu Hua Tseng
Section on Obesity and Hormone Action, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
Nature 454:1000-4. 2008..These data reveal an important role of BMP7 in promoting brown adipocyte differentiation and thermogenesis in vivo and in vitro, and provide a potential new therapeutic approach for the treatment of obesity...
Research Grants
- ROLE OF INSULIN AND IGF-1 ON BROWN ADIPOCYTESYu Hua Tseng; Fiscal Year: 2003..Accomplishment of the proposed studies will further our understanding on hormonal controls of metabolism and survival of brown adipocytes. ..
- Role of BMPs on Brown Adipogenesis and ThermogenesisYu Hua Tseng; Fiscal Year: 2006..abstract_text> ..
- Role of BMPs in Adipogenesis, Mitochondrial Function and Energy HomeostasisYu Hua Tseng; Fiscal Year: 2010..These studies will increase our understanding of adipocyte differentiation, energy balance, and BMP actions, and may help to develop potential therapeutic approaches for obesity and related diseases. ..
- Role of BMPs in Adipogenesis, Mitochondrial Function and Energy HomeostasisYu Hua Tseng; Fiscal Year: 2010..These studies will increase our understanding of adipocyte differentiation, energy balance, and BMP actions, and may help to develop potential therapeutic approaches for obesity and related diseases. ..