Gene Symbol: Sirt4
Description: sirtuin 4
Alias: NAD-dependent protein lipoamidase sirtuin-4, mitochondrial, NAD-dependent ADP-ribosyltransferase sirtuin-4, NAD-dependent protein deacetylase sirtuin-4
Species: rat
Products:     Sirt4

Top Publications

  1. 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
    ..are associated with heterochromatic regions and nucleoli, respectively, where yeast Sir2 functions; 2) SIRT3, SIRT4, and SIRT5 are localized in mitochondria, an organelle that links aging and energy metabolism; 3) cellular p53 is ..
  2. Laurent G, German N, Saha A, de Boer V, Davies M, Koves T, et al. SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase. Mol Cell. 2013;50:686-98 pubmed publisher
    ..In this study, we identify the mitochondrial sirtuin, SIRT4, as a regulator of lipid homeostasis...
  3. 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
    ..contrast, no mitochondrial hyperacetylation was detectable in mice lacking the two other mitochondrial sirtuins, SIRT4 and SIRT5...
  4. Jeong S, Xiao C, Finley L, Lahusen T, Souza A, Pierce K, et al. SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism. Cancer Cell. 2013;23:450-63 pubmed publisher
    ..This block requires the mitochondrial SIRT4, which is induced by numerous genotoxic agents and represses the metabolism of glutamine into tricarboxylic acid ..
  5. Csibi A, Fendt S, Li C, Poulogiannis G, Choo A, Chapski D, et al. The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4. Cell. 2013;153:840-54 pubmed publisher
    ..This regulation requires transcriptional repression of SIRT4, the mitochondrial-localized sirtuin that inhibits GDH...
  6. Liu B, Che W, Xue J, Zheng C, Tang K, Zhang J, et al. SIRT4 prevents hypoxia-induced apoptosis in H9c2 cardiomyoblast cells. Cell Physiol Biochem. 2013;32:655-62 pubmed publisher
    ..Here, we report that the expression of SIRT4, a mitochondrial sirtuin, is markedly down-regulated in hypoxia-induced apoptosis of H9c2 cardiomyoblast cells...
  7. Ramatchandirin B, Sadasivam M, Kannan A, Prahalathan C. Sirtuin 4 Regulates Lipopolysaccharide Mediated Leydig Cell Dysfunction. J Cell Biochem. 2016;117:904-16 pubmed publisher
    ..The present study demonstrates that LPS causes mitochondrial dysfunction via suppression of sirtuin 4 (SIRT4); which in turn affects Leydig cell function by modulating steroidogenesis and apoptosis...
  8. Haigis M, Mostoslavsky R, Haigis K, Fahie K, Christodoulou D, Murphy A, et al. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell. 2006;126:941-54 pubmed
    ..Mammals have seven Sir2 homologs (SIRT1-7). We show that SIRT4 is a mitochondrial enzyme that uses NAD to ADP-ribosylate and downregulate glutamate dehydrogenase (GDH) activity...
  9. 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
    ..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...

More Information


  1. Yu W, Zhou H, Lin R, Fu Y, Wang W. Short?term calorie restriction activates SIRT1?4 and ?7 in cardiomyocytes in vivo and in vitro. Mol Med Rep. 2014;9:1218-24 pubmed publisher
    ..These results suggest that CR may attenuate age?associated changes through reducing BW. Moreover, short?term CR may activate SIRT1 as well as SIRT2?4 and ?7 expression in cardiomyocytes in vivo and in vitro. ..
  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
    ..We report that human SIRT4 is localized to the mitochondria...
  3. Chen Y, Fang S, Fu Y, Zhou X, Xu M, Xu W. Calorie restriction on insulin resistance and expression of SIRT1 and SIRT4 in rats. Biochem Cell Biol. 2010;88:715-22 pubmed publisher
    ..Sirtuin 1 (SIRT1) and sirtuin 4 (SIRT4) have been reported to regulate insulin secretion, but their association with the development of insulin ..
  4. Komlos D, Mann K, Zhuo Y, Ricupero C, Hart R, Liu A, et al. Glutamate dehydrogenase 1 and SIRT4 regulate glial development. Glia. 2013;61:394-408 pubmed publisher
    ..regulated by many factors, and has been shown to be inhibited by the ADP-ribosyltransferase sirtuin 4 (SIRT4), a mitochondrially localized sirtuin. Here we show that SIRT4 is localized to mitochondria within the brain...
  5. Laurent G, de Boer V, Finley L, Sweeney M, Lu H, Schug T, et al. SIRT4 represses peroxisome proliferator-activated receptor ? activity to suppress hepatic fat oxidation. Mol Cell Biol. 2013;33:4552-61 pubmed publisher
    ..We have uncovered a novel role for the mitochondrial sirtuin SIRT4 in the regulation of hepatic lipid metabolism during changes in nutrient availability...
  6. Mathias R, Greco T, Oberstein A, Budayeva H, Chakrabarti R, Rowland E, et al. Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity. Cell. 2014;159:1615-25 pubmed publisher
    ..Despite conserved deacetylase domains, mitochondrial SIRT4 and SIRT5 have little to no deacetylase activity, and a robust catalytic activity for SIRT4 has been elusive...
  7. Verdin E. NAD⁺ in aging, metabolism, and neurodegeneration. Science. 2015;350:1208-13 pubmed publisher
    ..Here we review factors that regulate NAD(+) and discuss how supplementation with NAD(+) precursors may represent a new therapeutic opportunity for aging and its associated disorders, particularly neurodegenerative diseases. ..