SIRT5

Summary

Gene Symbol: SIRT5
Description: sirtuin 5
Alias: SIR2L5, NAD-dependent protein deacylase sirtuin-5, mitochondrial, NAD-dependent deacetylase sirtuin-5, NAD-dependent lysine demalonylase and desuccinylase sirtuin-5, mitochondrial, silent mating type information regulation 2, S.cerevisiae, homolog 5, sir2-like 5, sirtuin type 5
Species: human
Products:     SIRT5

Top Publications

  1. Frye R. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun. 2000;273:793-8 pubmed
    ..The seven human sirtuin genes include all four classes: SIRT1, SIRT2, and SIRT3 are class I, SIRT4 is class II, SIRT5 is class III, and SIRT6 and SIRT7 are class IV.
  2. Ahuja N, Schwer B, Carobbio S, Waltregny D, North B, Castronovo V, et al. Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase. J Biol Chem. 2007;282:33583-92 pubmed
    ..Depletion of SIRT4 from insulin-producing INS-1E cells results in increased insulin secretion in response to glucose. These observations define a new role for mitochondrial SIRT4 in the regulation of insulin secretion. ..
  3. Du J, Zhou Y, Su X, Yu J, Khan S, Jiang H, et al. Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science. 2011;334:806-9 pubmed publisher
    ..Four of them (Sirt4 to Sirt7) have no detectable or very weak deacetylase activity. We found that Sirt5 is an efficient protein lysine desuccinylase and demalonylase in vitro...
  4. Lai C, Lin P, Lin S, Hsu C, Lin H, Hu M, et al. Altered expression of SIRT gene family in head and neck squamous cell carcinoma. Tumour Biol. 2013;34:1847-54 pubmed publisher
    ..Our results demonstrated that the expression levels of SIRT1, SIRT2, SIRT3, SIRT5, SIRT6, and SIRT7 were significantly downregulated in cancerous tissues compared with noncancerous tissues (all p&..
  5. Lin Z, Xu H, Wang J, Lin Q, Ruan Z, Liu F, et al. SIRT5 desuccinylates and activates SOD1 to eliminate ROS. Biochem Biophys Res Commun. 2013;441:191-5 pubmed publisher
    ..Here, we report that SOD1 is succinylated and that succinylation decreases its activity. SIRT5 binds to, desuccinylates and activates SOD1. SOD1-mediated ROS reduction is increased when SIRT5 is co-expressed...
  6. Matsushita N, Yonashiro R, Ogata Y, Sugiura A, Nagashima S, Fukuda T, et al. Distinct regulation of mitochondrial localization and stability of two human Sirt5 isoforms. Genes Cells. 2011;16:190-202 pubmed publisher
    ..In this study, we clarified the mechanism of subcellular localization of two SIRT5 isoforms (i.e...
  7. Tan M, Peng C, Anderson K, Chhoy P, Xie Z, Dai L, et al. Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab. 2014;19:605-17 pubmed publisher
    ..We demonstrated that the previously annotated deacetylase, sirtuin 5 (SIRT5), is a lysine deglutarylase...
  8. Mahlknecht U, Ho A, Letzel S, Voelter Mahlknecht S. Assignment of the NAD-dependent deacetylase sirtuin 5 gene (SIRT5) to human chromosome band 6p23 by in situ hybridization. Cytogenet Genome Res. 2006;112:208-12 pubmed
    Sirtuin 5 (SIRT5) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase and belongs to the Silent information regulator 2 (Sir2) family of sirtuin histone deacetylases (HDACs), which play a central role in epigenetic gene ..
  9. Schlicker C, Gertz M, Papatheodorou P, Kachholz B, Becker C, Steegborn C. Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. J Mol Biol. 2008;382:790-801 pubmed publisher
    ..Mammalian mitochondria contain three Sirtuins, Sirt3, Sirt4, and Sirt5. Only one substrate is known for Sirt3 as well as for Sirt4, and up to now, no target for Sirt5 has been reported...

More Information

Publications111 found, 100 shown here

  1. Peng C, Lu Z, Xie Z, Cheng Z, Chen Y, Tan M, et al. The first identification of lysine malonylation substrates and its regulatory enzyme. Mol Cell Proteomics. 2011;10:M111.012658 pubmed publisher
    ..In addition, we demonstrate that Sirt5, a member of the class III lysine deacetylases, can catalyze lysine demalonylation and lysine desuccinylation ..
  2. Park J, Chen Y, Tishkoff D, Peng C, Tan M, Dai L, et al. SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways. Mol Cell. 2013;50:919-30 pubmed publisher
    Protein function is regulated by diverse posttranslational modifications. The mitochondrial sirtuin SIRT5 removes malonyl and succinyl moieties from target lysines...
  3. Lin J, Lin J, Chen H, Chen T, Apte R. Combined SIRT3 and SIRT5 deletion is associated with inner retinal dysfunction in a mouse model of type 1 diabetes. Sci Rep. 2019;9:3799 pubmed publisher
    ..in mice with monoallelic Nampt deletion from rod photoreceptors, mice lacking SIRT3, and mice lacking SIRT5 and tested multiple components of retinal function with electroretinography...
  4. Shuai L, Zhang L, Li B, Tang C, Wu L, Li J, et al. SIRT5 Regulates Brown Adipocyte Differentiation and Browning of Subcutaneous White Adipose Tissue. Diabetes. 2019;: pubmed publisher
    ..Several epigenetic regulators can control brown adipocyte development. Here, we show that SIRT5, a member of the sirtuins, is required for brown adipocyte differentiation and essential for brown adipogenic gene ..
  5. Liu B, Che W, Zheng C, Liu W, Wen J, Fu H, et al. SIRT5: a safeguard against oxidative stress-induced apoptosis in cardiomyocytes. Cell Physiol Biochem. 2013;32:1050-9 pubmed publisher
    b>SIRT5 is located in the mitochondria, and plays a crucial role in the regulation of metabolic process and cellular apoptosis. Cardiomyocytes are abundant in mitochondria...
  6. 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
    SIRT3 and SIRT5 have been shown to regulate mitochondrial fatty acid oxidation but the molecular mechanisms behind the regulation are lacking...
  7. Elkhwanky M, Hakkola J. Extranuclear Sirtuins and Metabolic Stress. Antioxid Redox Signal. 2018;28:662-676 pubmed publisher
    Extranuclear sirtuins in cytosol (SIRT2) and mitochondria (SIRT3, SIRT4, and SIRT5) are key regulators of metabolic enzymes and the antioxidative defense mechanisms...
  8. Gong J, Wang H, Lou W, Wang G, Tao H, Wen H, et al. Associations of sirtuins with clinicopathological parameters and prognosis in non-small cell lung cancer. Cancer Manag Res. 2018;10:3341-3356 pubmed publisher
    ..SIRT1, SIRT3, SIRT4, and SIRT7 were highly expressed in adeno-carcinoma (ADC) patients and female patients while SIRT5 were highly expressed in squamous cell carcinoma (SCC) patients and male patients...
  9. Hong J, Wang X, Mei C, Zan L. Competitive regulation by transcription factors and DNA methylation in the bovine SIRT5 promoter: Roles of E2F4 and KLF6. Gene. 2019;684:39-46 pubmed publisher
    Sirtuin 5 (SIRT5) belongs to the mitochondrial sirtuin family, which constitutes a highly conserved family of nicotinamide adenine dinucleotide NAD+-dependent deacetylases and ADP-ribosyltransferases that play important ..
  10. Rouble A, Storey K. Characterization of the SIRT family of NAD+-dependent protein deacetylases in the context of a mammalian model of hibernation, the thirteen-lined ground squirrel. Cryobiology. 2015;71:334-43 pubmed publisher
    ..To assess this possibility, protein levels of the seven mammalian SIRTs (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6 and SIRT7), total SIRT activity, and the acetylation status of two downstream SIRT targets (SOD2K68 and NF-..
  11. Bentley N, Fiveash C, Osborne B, Quek L, Ogura M, Inagaki N, et al. Protein hypoacylation induced by Sirt5 overexpression has minimal metabolic effect in mice. Biochem Biophys Res Commun. 2018;503:1349-1355 pubmed publisher
    ..Mammals have 7 sirtuins, which are located in different cellular compartments. Sirt5, a sirtuin isoform located in multiple subcellular sites, is involved in regulating a diverse range of cellular ..
  12. Bao X, Xiong Y, Li X, Li X. A chemical reporter facilitates the detection and identification of lysine HMGylation on histones. Chem Sci. 2018;9:7797-7801 pubmed publisher
    ..Using HMGAM-yne, we also identified Sirt5 as an 'eraser' that regulates HMGylation in cells...
  13. Zang W, Hao Y, Wang Z, Zheng W. Novel thiourea-based sirtuin inhibitory warheads. Bioorg Med Chem Lett. 2015;25:3319-24 pubmed publisher
    ..respectively, also behaved as strong inhibitory warheads against SIRT1/2/3 and SIRT5, typical deacetylases and deacylase in the human sirtuin family, respectively...
  14. Du Y, Hu H, Qu S, Wang J, Hua C, Zhang J, et al. SIRT5 deacylates metabolism-related proteins and attenuates hepatic steatosis in ob/ob mice. EBioMedicine. 2018;36:347-357 pubmed publisher
    Sirtuin 5 (SIRT5) is a NAD+-dependent lysine deacylase. The SIRT5 deficiency mouse model shows that it is dispensable for metabolic homeostasis under normal conditions...
  15. Hang T, Chen W, Wu M, Zhan L, Wang C, Jia N, et al. Structural insights into the molecular mechanism underlying Sirt5-catalyzed desuccinylation of histone peptides. Biochem J. 2019;476:211-223 pubmed publisher
    ..Here, we demonstrate that human sirtuin 5 (Sirt5) catalyzes the sequence-selective desuccinylation of numerous histone succinyl sites...
  16. Yang L, Ma X, He Y, Yuan C, Chen Q, Li G, et al. Sirtuin 5: a review of structure, known inhibitors and clues for developing new inhibitors. Sci China Life Sci. 2017;60:249-256 pubmed publisher
    ..Very recently, sirtuin 5 (SIRT5) has received considerable attention due to that it was found to have weak deacetylase activity but strong ..
  17. Nishida Y, Rardin M, Carrico C, He W, Sahu A, Gut P, et al. SIRT5 Regulates both Cytosolic and Mitochondrial Protein Malonylation with Glycolysis as a Major Target. Mol Cell. 2015;59:321-32 pubmed publisher
    Protein acylation links energetic substrate flux with cellular adaptive responses. SIRT5 is a NAD(+)-dependent lysine deacylase and removes both succinyl and malonyl groups...
  18. Igci M, Kalender M, Borazan E, Bozgeyik I, Bayraktar R, Bozgeyik E, et al. High-throughput screening of Sirtuin family of genes in breast cancer. Gene. 2016;586:123-8 pubmed publisher
    ..In contrast, SIRT2, SIRT3, and SIRT5 genes were shown to be up-regulated in our study...
  19. Qin K, Han C, Zhang H, Li T, Li N, Cao X. NAD+ dependent deacetylase Sirtuin 5 rescues the innate inflammatory response of endotoxin tolerant macrophages by promoting acetylation of p65. J Autoimmun. 2017;81:120-129 pubmed publisher
    ..expression and function of NAD+ dependent type III deacetylase Sirtuin family members, we found that SIRT5 and SIRT1/2 had opposite expression patterns and functions in macrophages...
  20. Maeda S, Koya D, Araki S, Babazono T, Umezono T, Toyoda M, et al. Association between single nucleotide polymorphisms within genes encoding sirtuin families and diabetic nephropathy in Japanese subjects with type 2 diabetes. Clin Exp Nephrol. 2011;15:381-390 pubmed publisher
    ..We examined 52 SNPs within the SIRT genes (11 in SIRT1, 7 in SIRT2, 14 in SIRT3, 7 in SIRT4, 9 in SIRT5, and 4 in SIRT6) in 3 independent Japanese populations with type 2 diabetes (study 1: 747 cases (overt proteinuria)..
  21. Lv X, Liu L, Cheng C, Yu B, Xiong L, Hu K, et al. SUN2 exerts tumor suppressor functions by suppressing the Warburg effect in lung cancer. Sci Rep. 2015;5:17940 pubmed publisher
    ..Finally, our results provided evidence that SIRT5 acts, at least partly, as a negative regulator of SUN2...
  22. Sadhukhan S, Liu X, Ryu D, Nelson O, Stupinski J, Li Z, et al. Metabolomics-assisted proteomics identifies succinylation and SIRT5 as important regulators of cardiac function. Proc Natl Acad Sci U S A. 2016;113:4320-5 pubmed publisher
    ..One such PTM is lysine succinylation, which is regulated by sirtuin 5 (SIRT5)...
  23. Simic Z, Weiwad M, Schierhorn A, Steegborn C, Schutkowski M. The É›-Amino Group of Protein Lysine Residues Is Highly Susceptible to Nonenzymatic Acylation by Several Physiological Acyl-CoA Thioesters. Chembiochem. 2015;16:2337-47 pubmed publisher
    ..that SIRT3 exhibits deacetylase activity but is not able to remove any of the succinyl groups from CypA, whereas SIRT5 is an effective protein desuccinylase...
  24. Temel M, Koç M, Ulutaş S, Göğebakan B. The expression levels of the sirtuins in patients with BCC. Tumour Biol. 2016;37:6429-35 pubmed publisher
    ..1, Sirt1.2, Sirt2, Sirt3, Sirt4, Sirt5, Sirt6, and Sirt7) were examined by real-time PCR. The results showed that expressions of SIRT1.1, SIRT1...
  25. Hsu Y, Wu Y, Yu T, Wei Y. Mitochondria in mesenchymal stem cell biology and cell therapy: From cellular differentiation to mitochondrial transfer. Semin Cell Dev Biol. 2016;52:119-31 pubmed publisher
    ..Importantly, we provide evidence to suggest that alteration in the expression of Sirt3 and Sirt5 and relative changes in the acylation levels of mitochondrial proteins might be involved in the activation of ..
  26. Motyl J, Wencel P, Cieslik M, Strosznajder R, Strosznajder J. Alpha-synuclein alters differently gene expression of Sirts, PARPs and other stress response proteins: implications for neurodegenerative disorders. Mol Neurobiol. 2018;55:727-740 pubmed publisher
    ..Moreover, eASN upregulated expression of Sirt3 and Sirt5, but downregulated of Sirt1, which plays an important role in cell metabolism including Aβ precursor protein (APP)..
  27. Aguilo F, Li S, Balasubramaniyan N, Sancho A, Benko S, Zhang F, et al. Deposition of 5-Methylcytosine on Enhancer RNAs Enables the Coactivator Function of PGC-1α. Cell Rep. 2016;14:479-492 pubmed publisher
    ..loss of Set7/9 and NSun7 in liver cell model systems resulted in depletion of the PGC-1α target genes Pfkl, Sirt5, Idh3b, and Hmox2, which was accompanied by a decrease in the eRNAs levels associated with these loci...
  28. Parihar P, Solanki I, Mansuri M, Parihar M. Mitochondrial sirtuins: emerging roles in metabolic regulations, energy homeostasis and diseases. Exp Gerontol. 2015;61:130-41 pubmed publisher
    ..Mitochondria inhabit three main types of sirtuins classified as Sirt3, Sirt4 and Sirt5. These sirtuins regulate mitochondrial metabolic functions mainly through controlling post-translational ..
  29. Wong D, Soga T, Parhar I. Aging and chronic administration of serotonin-selective reuptake inhibitor citalopram upregulate Sirt4 gene expression in the preoptic area of male mice. Front Genet. 2015;6:281 pubmed publisher
    ..Age-related increases of sirt1, sirt4, sirt5, and sirt7 mRNA levels were observed in the POA of 52 weeks old mice...
  30. Chen Y. Quantitative Analysis of the Sirt5-Regulated Lysine Succinylation Proteome in Mammalian Cells. Methods Mol Biol. 2016;1410:23-37 pubmed publisher
    ..It is regulated by Sirt5, a member of the class III histone deacetylases (HDACs) or the Sirtuins...
  31. Omonijo O, Wongprayoon P, Ladenheim B, McCoy M, Govitrapong P, Jayanthi S, et al. Differential effects of binge methamphetamine injections on the mRNA expression of histone deacetylases (HDACs) in the rat striatum. Neurotoxicology. 2014;45:178-84 pubmed publisher
    ..The expression of the class IV HDAC, HDAC11, was also suppressed by METH. The expression of Sirt2, Sirt5, and Sirt6 that are members of class III HDACs was also downregulated by METH injections...
  32. Wang Y, Jin J, Chung M, Feng L, Sun H, Hao Q. Identification of the YEATS domain of GAS41 as a pH-dependent reader of histone succinylation. Proc Natl Acad Sci U S A. 2018;115:2365-2370 pubmed publisher
    ..Following our previous study of SIRT5 as an eraser of succinyl-lysine (Ksuc), here we identified the GAS41 YEATS domain as a reader of Ksuc on histones...
  33. Li Y, Huang W, You L, Xie T, He B. A FRET-based assay for screening SIRT5 specific modulators. Bioorg Med Chem Lett. 2015;25:1671-1674 pubmed publisher
    A fluorogenic assay for SIRT5 has been developed to screen their small molecule modulators based on the recent discovery that SIRT5 is a demalonylase and desuccinylase...
  34. Gui L, Wang H, Liu G, Zan L. Polymorphisms in the SIRT5 gene and their association with body measurement and ultrasound traits in Qinchuan cattle. Genet Mol Res. 2015;14:3843-53 pubmed publisher
    Silent information regulator 5 (SIRT5), a member of the Sirtuin family class III nicotinamide adenine dinucleotide-dependent protein deacetylases, plays an important role in metabolic and aging processes in mammals...
  35. Hong J, Zhang X, Lin H. HPLC-Based Enzyme Assays for Sirtuins. Methods Mol Biol. 2018;1813:225-234 pubmed publisher
    ..HPLC)-based method to measure the enzyme kinetics for SIRT2 and SIRT6's demyristoylase activities and SIRT5's desuccinylase activity...
  36. Dang S, Zhou J, Wang Z, Wang K, Dai S, He S. MiR-299-3p functions as a tumor suppressor via targeting Sirtuin 5 in hepatocellular carcinoma. Biomed Pharmacother. 2018;106:966-975 pubmed publisher
    ..PCR, Pearson's correlation coefficient analysis, immunohistochemistry and Western blot showed that Sirtuin 5 (SIRT5) was a downstream target of miR-299-3p in HCC cells...
  37. Guetschow E, Kumar S, Lombard D, Kennedy R. Identification of sirtuin 5 inhibitors by ultrafast microchip electrophoresis using nanoliter volume samples. Anal Bioanal Chem. 2016;408:721-31 pubmed publisher
    Sirtuin 5 (SIRT5) is a member of the sirtuin family of protein deacylases that catalyzes removal of post-translational modifications, such as succinyl and malonyl moieties, on lysine residues...
  38. Fernández Coto D, Gil J, Hernandez A, Herrera Goepfert R, Castro Romero I, Hernandez Marquez E, et al. Quantitative proteomics reveals proteins involved in the progression from non-cancerous lesions to gastric cancer. J Proteomics. 2018;186:15-27 pubmed publisher
    ..The impairment of mitochondrial pathways was correlated with down-regulation of SIRT3 and SIRT5, and overexpression of enzymes supporting the glycolytic phenotype, such as HK3 and PCK2...
  39. Wang Y, Liu Q, Huan Y, Li R, Li C, Sun S, et al. Sirtuin 5 overexpression attenuates glucolipotoxicity-induced pancreatic ? cells apoptosis and dysfunction. Exp Cell Res. 2018;371:205-213 pubmed publisher
    Recently, SIRT5 was reported to be a predominant desuccinylase and demalonylase in mitochondria...
  40. Chen X, Tian M, Sun R, Zhang M, Zhou L, Jin L, et al. SIRT5 inhibits peroxisomal ACOX1 to prevent oxidative damage and is downregulated in liver cancer. EMBO Rep. 2018;19: pubmed publisher
    ..Here, we show that the deacetylase sirtuin 5 (SIRT5) is present in peroxisomes and that ACOX1 is a physiological substrate of SIRT5...
  41. He Y, Yan L, Zang W, Zheng W. Novel sirtuin inhibitory warheads derived from the N(ε)-acetyl-lysine analog L-2-amino-7-carboxamidoheptanoic acid. Org Biomol Chem. 2015;13:10442-50 pubmed publisher
    ..4-6.6-fold stronger SIRT1/2/3 inhibitory warhead than L-ACAH. Carboxamide NH2-dodecylated and carboxymethylated analogs of L-ACAH were also identified as potent SIRT6 and SIRT5 inhibitory warheads, respectively.
  42. Kida Y, Goligorsky M. Sirtuins, Cell Senescence, and Vascular Aging. Can J Cardiol. 2016;32:634-41 pubmed publisher
    ..SIRT1 and SIRT2 are localized in the nucleus and cytoplasm. SIRT3, SIRT4, and SIRT5 are mitochondrial, and SIRT6 and SIRT7 are nuclear...
  43. Wang F, Wang K, Xu W, Zhao S, Ye D, Wang Y, et al. SIRT5 Desuccinylates and Activates Pyruvate Kinase M2 to Block Macrophage IL-1? Production and to Prevent DSS-Induced Colitis in Mice. Cell Rep. 2017;19:2331-2344 pubmed publisher
    ..Here, we show that PKM2 is a physiological substrate of SIRT5 and that SIRT5-regulated hypersuccinylation inhibits the pyruvate kinase activity of PKM2 by promoting its ..
  44. Carrico C, Meyer J, He W, Gibson B, Verdin E. The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications. Cell Metab. 2018;27:497-512 pubmed publisher
    ..Three protein deacylases, SIRT3, SIRT4, and SIRT5, reside in the mitochondria and remove these modifications from targeted proteins in an NAD+-dependent ..
  45. Du Z, Liu X, Chen T, Gao W, Wu Z, Hu Z, et al. Targeting a Sirt5-Positive Subpopulation Overcomes Multidrug Resistance in Wild-Type Kras Colorectal Carcinomas. Cell Rep. 2018;22:2677-2689 pubmed publisher
    ..of multidrug resistance in wild-type Kras CRCs based on the survival of a cell subpopulation characterized by Sirt5 expression...
  46. Hershberger K, Abraham D, Liu J, Locasale J, Grimsrud P, Hirschey M. Ablation of Sirtuin5 in the postnatal mouse heart results in protein succinylation and normal survival in response to chronic pressure overload. J Biol Chem. 2018;293:10630-10645 pubmed publisher
    Mitochondrial Sirtuin 5 (SIRT5) is an NAD+-dependent demalonylase, desuccinylase, and deglutarylase that controls several metabolic pathways...
  47. Li F, Liu L. SIRT5 Deficiency Enhances Susceptibility to Kainate-Induced Seizures and Exacerbates Hippocampal Neurodegeneration not through Mitochondrial Antioxidant Enzyme SOD2. Front Cell Neurosci. 2016;10:171 pubmed publisher
    ..Sirtuin 5 (SIRT5), localized in mitochondrial matrix, has been considered as an important functional modulator of mitochondria that ..
  48. Boylston J, Sun J, Chen Y, Gucek M, Sack M, Murphy E. Characterization of the cardiac succinylome and its role in ischemia-reperfusion injury. J Mol Cell Cardiol. 2015;88:73-81 pubmed publisher
    Succinylation refers to modification of lysine residues with succinyl groups donated by succinyl-CoA. Sirtuin5 (Sirt5) is a mitochondrial NAD(+)-dependent deacylase that catalyzes the removal of succinyl groups from proteins...
  49. Guedouari H, Daigle T, Scorrano L, Hébert Chatelain E. Sirtuin 5 protects mitochondria from fragmentation and degradation during starvation. Biochim Biophys Acta Mol Cell Res. 2017;1864:169-176 pubmed publisher
    ..Here we show that the mitochondrial Sirtuin 5 (Sirt5) is essential for starvation induced mitochondrial elongation...
  50. Liu L, Peritore C, Ginsberg J, Shih J, Arun S, Donmez G. Protective role of SIRT5 against motor deficit and dopaminergic degeneration in MPTP-induced mice model of Parkinson's disease. Behav Brain Res. 2015;281:215-21 pubmed publisher
    ..b>SIRT5, which localizes in the mitochondrial matrix, is nicotinamide adenine dinucleotide (NAD(+))-dependent histone ..
  51. Dall M, Penke M, Sulek K, Matz Soja M, Holst B, Garten A, et al. Hepatic NAD+ levels and NAMPT abundance are unaffected during prolonged high-fat diet consumption in C57BL/6JBomTac mice. Mol Cell Endocrinol. 2018;473:245-256 pubmed publisher
    ..This decrease was not associated with changes in SIRT5 abundance...
  52. Tanabe K, Liu J, Kato D, Kurumizaka H, Yamatsugu K, Kanai M, et al. LC-MS/MS-based quantitative study of the acyl group- and site-selectivity of human sirtuins to acylated nucleosomes. Sci Rep. 2018;8:2656 pubmed publisher
    ..The acyl group- and site-selectivity of each sirtuin is unique to its subtype. Sirt5 exclusively removes negatively-charged acyl groups, while Sirt1/2/3/6/7 preferentially remove hydrophobic acyl ..
  53. Lim R, Barker G, Menon R, Lappas M. A Novel Role for SIRT3 in Regulating Mediators Involved in the Terminal Pathways of Human Labor and Delivery. Biol Reprod. 2016;95:95 pubmed
    ..In this study, we determined the effect of term labor and pro-inflammatory cytokines on SIRT3, SIRT4, SIRT5, and SIRT7 expression in human myometrium...
  54. Khojah S, Payne A, McGuinness D, Shiels P. Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat. Cells. 2016;5: pubmed
    ..We have used biomarkers of aging (SA ?-Gal, p16Ink4a, Sirt5, Sirt6, and Sirt7) to demonstrate the presence of an accelerated aging phenotype across different brain regions in ..
  55. Celichowski P, Jopek K, Szyszka M, Tyczewska M, Malendowicz L, Rucinski M. Mitochondrial sirtuins in the rat adrenal gland: location within the glands of males and females, hormonal and developmental regulation of gene expressions. Folia Histochem Cytobiol. 2017;55:190-202 pubmed publisher
    ..These findings suggest that sirtuins expressed in mitochondria, Sirt3, Sirt4 and Sirt5, may be associated with adrenal steroidogenesis...
  56. Li L, Zhang P, Bao Z, Wang T, Liu S, Huang F. PGC-1? Promotes Ureagenesis in Mouse Periportal Hepatocytes through SIRT3 and SIRT5 in Response to Glucagon. Sci Rep. 2016;6:24156 pubmed publisher
    ..showed that fasting strongly stimulated mice glucagon secretion, hepatic PGC-1?, sirtuin 3 (SIRT3) and sirtuin 5 (SIRT5) expression and ureagenesis enzymatic activity such as carbamoyl phosphate synthetase 1 (CPS1) and ornithine ..
  57. Hong S, Ng L, Ng L, Inoue T, Tolwinski N, Hagen T, et al. The Role of Mitochondrial Non-Enzymatic Protein Acylation in Ageing. PLoS ONE. 2016;11:e0168752 pubmed publisher
    ..Rats have two substrate-specific mitochondrial deacylases, SIRT3 and SIRT5 while both flies and worms lack these enzymes...
  58. Diaz Cañestro C, Merlini M, Bonetti N, Liberale L, Wüst P, Briand Schumacher S, et al. Sirtuin 5 as a novel target to blunt blood-brain barrier damage induced by cerebral ischemia/reperfusion injury. Int J Cardiol. 2018;260:148-155 pubmed publisher
    ..This study sought to determine whether SIRT5 contributes to BBB damage following I/R brain injury...
  59. Du Y, Hu H, Hua C, Du K, Wei T. Tissue distribution, subcellular localization, and enzymatic activity analysis of human SIRT5 isoforms. Biochem Biophys Res Commun. 2018;503:763-769 pubmed publisher
    b>SIRT5 is one of the seven mammalian sirtuins which are NAD+-dependent deacylases...
  60. Chen L, Wang H, Gao F, Zhang J, Zhang Y, Ma R, et al. Functional genetic variants in the SIRT5 gene promoter in acute myocardial infarction. Gene. 2018;675:233-239 pubmed publisher
    ..Mitochondrial sirtuins, SIRT3, SIRT4 and SIRT5, function as critical regulators of mitochondrial metabolism, oxidative stress and cell survival...
  61. Lutz M, Milenkovic I, Regelsberger G, Kovacs G. Distinct patterns of sirtuin expression during progression of Alzheimer's disease. Neuromolecular Med. 2014;16:405-14 pubmed publisher
    ..loss of neuroprotection dependent on the neuronal population; (2) in contrast to SIRT1 and 3, expression of SIRT5 increases during the progression of AD; (3) which might be related to its appearance in activated microglial cells...
  62. Lu W, Zuo Y, Feng Y, Zhang M. SIRT5 facilitates cancer cell growth and drug resistance in non-small cell lung cancer. Tumour Biol. 2014;35:10699-705 pubmed publisher
    ..Here we show that the mitochondrial class III NAD(+)-dependent deacetylase SIRT5 is overexpressed in human NSCLC and high expression of SIRT5 predicts poor survival...
  63. Yamamoto H, Schoonjans K, Auwerx J. Sirtuin functions in health and disease. Mol Endocrinol. 2007;21:1745-55 pubmed
    ..Here, we review some of the recent data related to the sirtuins and discuss their mode of action, their biological role in cellular and organismal models, and their possible association to age-related human diseases. ..
  64. Kawahara T, Michishita E, Adler A, Damian M, Berber E, Lin M, et al. SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span. Cell. 2009;136:62-74 pubmed publisher
    ..We propose that SIRT6 attenuates NF-kappaB signaling via H3K9 deacetylation at chromatin, and hyperactive NF-kappaB signaling may contribute to premature and normal aging. ..
  65. Tang X, Chen X, Chen H, Liu D. Mitochondrial Sirtuins in cardiometabolic diseases. Clin Sci (Lond). 2017;131:2063-2078 pubmed publisher
    ..Three members of the Sirtuin family (SIRT3, SIRT4, and SIRT5) are located in the mitochondrion...
  66. Polletta L, Vernucci E, Carnevale I, Arcangeli T, Rotili D, Palmerio S, et al. SIRT5 regulation of ammonia-induced autophagy and mitophagy. Autophagy. 2015;11:253-70 pubmed publisher
    In liver the mitochondrial sirtuin, SIRT5, controls ammonia detoxification by regulating CPS1, the first enzyme of the urea cycle...
  67. Preyat N, Rossi M, Kers J, Chen L, Bertin J, Gough P, et al. Intracellular nicotinamide adenine dinucleotide promotes TNF-induced necroptosis in a sirtuin-dependent manner. Cell Death Differ. 2016;23:29-40 pubmed publisher
    ..knockdown led us to uncover a role for the NAD(+)-dependent family of sirtuins, and in particular for SIRT2 and SIRT5, in the regulation of the necroptotic cell death program...
  68. Liang F, Wang X, Ow S, Chen W, Ong W. Sirtuin 5 is Anti-apoptotic and Anti-oxidative in Cultured SH-EP Neuroblastoma Cells. Neurotox Res. 2017;31:63-76 pubmed publisher
    ..adenine dinucleotide (NAD+)-dependent deacetylase, demalonylase, and desuccinylase, sirtuin 5 (SIRT5) in host cells has been reportedly observed in the mitochondria, in the cytosol/cytoplasm or in the nucleus...
  69. Lin J, Kubota S, Ban N, Yoshida M, Santeford A, Sene A, et al. NAMPT-Mediated NAD(+) Biosynthesis Is Essential for Vision In Mice. Cell Rep. 2016;17:69-85 pubmed publisher
    ..We further demonstrate that the NAD(+)-dependent mitochondrial deacylases SIRT3 and SIRT5 play important roles in retinal homeostasis and that NAD(+) deficiency causes SIRT3 dysfunction...
  70. Hershberger K, Abraham D, MARTIN A, Mao L, Liu J, Gu H, et al. Sirtuin 5 is required for mouse survival in response to cardiac pressure overload. J Biol Chem. 2017;292:19767-19781 pubmed publisher
    In mitochondria, the sirtuin SIRT5 is an NAD+-dependent protein deacylase that controls several metabolic pathways...
  71. Yang X, Wang Z, Li X, Liu B, Liu M, Liu L, et al. SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferation. Cancer Res. 2018;78:372-386 pubmed publisher
    ..Here, we report that the sirtuin SIRT5 desuccinylates SHMT2 to increase its activity and drive serine catabolism in tumor cells...
  72. Glorioso C, Oh S, Douillard G, Sibille E. Brain molecular aging, promotion of neurological disease and modulation by sirtuin 5 longevity gene polymorphism. Neurobiol Dis. 2011;41:279-90 pubmed publisher
    ..that subjects carrying a newly-characterized low-expressing polymorphism in a putative longevity gene (Sirtuin5; SIRT5(prom2)) have older brain molecular ages...
  73. Liu J, Huang Y, Zheng W. A Selective Cyclic Peptidic Human SIRT5 Inhibitor. Molecules. 2016;21: pubmed publisher
    ..residue behaved as a strong and selective (versus human SIRT1/2/3/6) inhibitor against human SIRT5-catalyzed deacylation reaction...
  74. Pannek M, Simic Z, Fuszard M, Meleshin M, Rotili D, Mai A, et al. Crystal structures of the mitochondrial deacylase Sirtuin 4 reveal isoform-specific acyl recognition and regulation features. Nat Commun. 2017;8:1513 pubmed publisher
    ..In contrast to the mitochondrial deacetylase Sirt3 and desuccinylase Sirt5, no prominent deacylase activity and structural information are available for Sirt4...
  75. de Moura M, Uppala R, Zhang Y, Van Houten B, Goetzman E. Overexpression of mitochondrial sirtuins alters glycolysis and mitochondrial function in HEK293 cells. PLoS ONE. 2014;9:e106028 pubmed publisher
    SIRT3, SIRT4, and SIRT5 are mitochondrial deacylases that impact multiple facets of energy metabolism and mitochondrial function...
  76. Chang L, Xi L, Liu Y, Liu R, Wu Z, Jian Z. SIRT5 promotes cell proliferation and invasion in hepatocellular carcinoma by targeting E2F1. Mol Med Rep. 2017;: pubmed publisher
    Sirtuin 5 (SIRT5) is a member of the NAD+?dependent class III protein deacetylases...
  77. Wang Y, Wang H, Xu J, Tan J, Fu L, Wang J, et al. Sirtuin5 contributes to colorectal carcinogenesis by enhancing glutaminolysis in a deglutarylation-dependent manner. Nat Commun. 2018;9:545 pubmed publisher
    ..Here we show that mitochondrial Sirtuin5 (SIRT5), which mediates lysine desuccinylation, deglutarylation, and demalonylation, plays a role in colorectal cancer (..
  78. Zhou Y, Zhang H, He B, Du J, Lin H, Cerione R, et al. The bicyclic intermediate structure provides insights into the desuccinylation mechanism of human sirtuin 5 (SIRT5). J Biol Chem. 2012;287:28307-14 pubmed publisher
    ..Their functions have been generally attributed to NAD-dependent deacetylase activity. However, human SIRT5 (sirtuin 5), which has been reported to exhibit little deacetylase activity, was recently identified as an NAD-..
  79. Roessler C, Nowak T, Pannek M, Gertz M, Nguyen G, Scharfe M, et al. Chemical probing of the human sirtuin 5 active site reveals its substrate acyl specificity and peptide-based inhibitors. Angew Chem Int Ed Engl. 2014;53:10728-32 pubmed publisher
    ..derived peptide substrate and modified the lysine side chain systematically to determine the acyl specificity of Sirt5. From that point we designed six potent peptide-based inhibitors that interact with the NAD(+) binding pocket...
  80. Kumar S, Lombard D. Generation and Purification of Catalytically Active Recombinant Sirtuin5 (SIRT5) Protein. Methods Mol Biol. 2016;1436:241-57 pubmed publisher
    Sirtuin-family deacylases promote health and longevity in mammals. The sirtuin SIRT5 localizes predominantly to the mitochondrial matrix...
  81. Shen X, Li P, Xu Y, Chen X, Sun H, Zhao Y, et al. Association of sirtuins with clinicopathological parameters and overall survival in gastric cancer. Oncotarget. 2017;8:74359-74370 pubmed publisher
    ..96, 95% CI = 1.63-2.35, P = 2.7E-13), whereas no significant association existed between SIRT5 mRNA expression and overall survival...
  82. Luo H, Zhou M, Ji K, Zhuang J, Dang W, Fu S, et al. Expression of Sirtuins in the Retinal Neurons of Mice, Rats, and Humans. Front Aging Neurosci. 2017;9:366 pubmed publisher
    ..On the other hand, none of the other Sirtuins exhibit any significant age-related changes in expression except for SIRT5, which was significantly higher in the retinas of adults compared to both young and aged rats...
  83. Guan D, Lim J, Peng L, Liu Y, Lam M, Seto E, et al. Deacetylation of the tumor suppressor protein PML regulates hydrogen peroxide-induced cell death. Cell Death Dis. 2014;5:e1340 pubmed publisher
    ..We found that hydrogen peroxide (H2O2) promotes PML deacetylation and identified SIRT1 and SIRT5 as PML deacetylases...
  84. Wu T, Liu Y, Fu Y, Liu X, Zhou X. Direct evidence of sirtuin downregulation in the liver of non-alcoholic fatty liver disease patients. Ann Clin Lab Sci. 2014;44:410-8 pubmed
    ..RT-PCR and Western blotting demonstrated decreased expression of SIRT1, SIRT3, SIRT5, and SIRT6 in the NAFLD group in comparison with the control group...
  85. Osborne B, Bentley N, Montgomery M, Turner N. The role of mitochondrial sirtuins in health and disease. Free Radic Biol Med. 2016;100:164-174 pubmed publisher
    ..SIRT3, SIRT4, and SIRT5 are found primarily located in the mitochondria, and are involved in many of the key processes of this organelle...
  86. Vasquez M, Beam M, Blackwell S, Zuzow M, Tomanek L. Sirtuins regulate proteomic responses near thermal tolerance limits in the blue mussels Mytilus galloprovincialis and Mytilus trossulus. J Exp Biol. 2017;220:4515-4534 pubmed publisher
    ..trossulus, respectively. Western blot analysis showed that the levels of mitochondrial sirtuin 5 (SIRT5) were generally three times higher and increased with acute heat stress in response to sirtuin inhibition in M...
  87. 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
    ..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 p53 is a major in ..
  88. Fischer F, Gertz M, Suenkel B, Lakshminarasimhan M, Schutkowski M, Steegborn C. Sirt5 deacylation activities show differential sensitivities to nicotinamide inhibition. PLoS ONE. 2012;7:e45098 pubmed publisher
    ..Using this assay, we show that the deacetylation activity of human Sirt5 features an unusual insensitivity to nicotinamide inhibition...
  89. Zhou L, Wang F, Sun R, Chen X, Zhang M, Xu Q, et al. SIRT5 promotes IDH2 desuccinylation and G6PD deglutarylation to enhance cellular antioxidant defense. EMBO Rep. 2016;17:811-22 pubmed publisher
    ..Here, we report that SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose-6-phosphate dehydrogenase (G6PD), ..
  90. Xiangyun Y, Xiaomin N, Linping G, Yunhua X, Ziming L, Yongfeng Y, et al. Desuccinylation of pyruvate kinase M2 by SIRT5 contributes to antioxidant response and tumor growth. Oncotarget. 2017;8:6984-6993 pubmed publisher
    ..Here we report that PKM2 is succinylated at lysine 498 (K498) and succinylation increases its activity. SIRT5 binds to, desuccinylates and inhibits PKM2 activity...
  91. Frye R. Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity. Biochem Biophys Res Commun. 1999;260:273-9 pubmed
    ..The SIRT1 sequence has the closest homology to the S. cerevisiae Sir2p. The SIRT4 and SIRT5 sirtuins more closely resemble prokaryotic sirtuin sequences...
  92. Matsushima S, Sadoshima J. The role of sirtuins in cardiac disease. Am J Physiol Heart Circ Physiol. 2015;309:H1375-89 pubmed publisher
    ..On the other hand, the roles of Sirt4 and Sirt5 in the heart remain largely uncharacterized.