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Literature summary for 2.3.1.B43 extracted from

  • Shuai, L.; Zhang, L.N.; Li, B.H.; Tang, C.L.; Wu, L.Y.; Li, J.; Li, J.Y.
    SIRT5 regulates brown adipocyte differentiation and browning of subcutaneous white adipose tissue (2019), Diabetes, 68, 1449-1461 .
    View publication on PubMed
Search for more literature for 2.3.1.B43

Cloned(Commentary)

Cloned (Comment) Organism
gene SIRT5, quantitative real-time PCR expression analysis Mus musculus

Protein Variants

Protein Variants Comment Organism
additional information generation of SIRT5 knockout mice on the Sv129 background using the lentiviral SIRT5 shRNA plasmid sc-63027-SH Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion primarily Mus musculus 5739
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Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Mus musculus SIRT5 modifies lysine succinylation, malonylation, and glutarylation ?
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NAD+ + [glucose 6-phosphate dehydrogenase]-N6-succinyl-L-lysine Mus musculus
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 nicotinamide + [glucose 6-phosphate dehydrogenase]-L-lysine + 2'-O-succinyl-ADP-ribose
-
 ?
NAD+ + [histone H2B]-N6-succinyl-L-lysine9 Mus musculus partial desuccinylation nicotinamide + [histone H2B]-L-lysine9 + 2'-O-succinyl-ADP-ribose
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 ?
NAD+ + [IDH2]-N6-succinyl-L-lysine Mus musculus i.e. isocitrate dehydrogenase [NADP+] nicotinamide + [IDH2]-L-lysine + 2'-O-succinyl-ADP-ribose
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 ?

Organism

Organism UniProt Comment Textmining
Mus musculus A0A1Y7VM56
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-

Source Tissue

Source Tissue Comment Organism Textmining
brown adipocyte
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 Mus musculus
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white adipocyte
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 Mus musculus
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information SIRT5 modifies lysine succinylation, malonylation, and glutarylation Mus musculus ?
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-
NAD+ + [glucose 6-phosphate dehydrogenase]-N6-succinyl-L-lysine
-
 Mus musculus nicotinamide + [glucose 6-phosphate dehydrogenase]-L-lysine + 2'-O-succinyl-ADP-ribose
-
 ?
NAD+ + [histone H2B]-N6-succinyl-L-lysine9 partial desuccinylation Mus musculus nicotinamide + [histone H2B]-L-lysine9 + 2'-O-succinyl-ADP-ribose
-
 ?
NAD+ + [IDH2]-N6-succinyl-L-lysine i.e. isocitrate dehydrogenase [NADP+] Mus musculus nicotinamide + [IDH2]-L-lysine + 2'-O-succinyl-ADP-ribose
-
 ?

Synonyms

Synonyms Comment Organism
SIRT5
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 Mus musculus

Cofactor

Cofactor Comment Organism Structure
NAD+
-
 Mus musculus

Expression

Organism Comment Expression
Mus musculus in subcutaneous inguinal white adipose tissue, only Sirt5 expression is significantly increased after cold exposure up

General Information

General Information Comment Organism
evolution sirtuins, which are class III histone deacetylases (HDACs), are an evolutionarily conserved family of NAD-dependent lysine deacetylases that play important roles in the regulation of aging, tumorigenesis, energy metabolism and stress resistance Mus musculus
malfunction SIRT5 knockout mice on the Sv129 background exhibit less browning capacity in subcutaneous white adipose tissue compared to controls and show apparent cold intolerance, suggesting that SIRT5 can modulate the browning process in vivo. Knockdown of SIRT5 impairs brown adipocyte differentiation of C3H10T1/2 multipotent mesenchymal cells and blocks adipogenic gene activation. Lipid accumulation and basal and uncoupled oxygen consumption rates are significantly reduced in SIRT5 knockdown cells. The expression levels of PPARgamma, PRDM16, and UCP1 are significantly augmented in the SIRT5 overexpression cells, which is consistent with the increased lipid accumulation. UCP1 expression is significantly increased in SIRT5 overexpression groups. Knockdown of SIRT5 reduces 2-oxoglutarate concentration and supplementation of 2-oxoglutarate partially rescues brown adipocyte differentiation in SIRT5 knockdown cells. Knockdown of SIRT5 results in increased H3K9me2 and H3K9me3 levels in the promoter regions of Ppargamma and Prdm16 Mus musculus
metabolism SIRT5 regulates brown adipogenic gene activation at least partly through an indirect effect on histone modifications, linkage between epigenetics and cell differentiation. SIRT5 is implicated in the urea cycle by activating carbamoyl phosphate synthetase 1. SIRT5 modifies lysine succinylation, malonylation, and glutarylation both inside and outside of the mitochondria and impacts multiple enzymes involved in diverse mitochondrial metabolic pathways. SIRT5 has crucial effects on cellular metabolite flux Mus musculus
physiological function adipose tissue plays a vital role in metabolic regulation. SIRT5 regulates brown adipocyte differentiation and browning of subcutaneous white adipose tissue. SIRT5 modifies lysine succinylation, malonylation, and glutarylation both inside and outside of the mitochondria. SIRT5 can desuccinylate and deglutarylate IDH2 and G6PD, respectively, thereby activating both enzymes to maintain cellular NADPH homeostasis and redox potential during oxidative stress. SIRT5 is essential for brown adipocyte differentiation in vitro and has an impact on browning of subcutaneous adipose tissue in vivo. SIRT5 may play an important role in adaptive thermogenesis of brown/beige adipocytes Mus musculus