Potential Modulation of Sirtuins by Oxidative Stress

Table 1

General characteristics of mammalian sirtuins.

Human isoforms	Localization	Length	Conserved catalytic core position	Catalytic activity	Substrate	Function	References
SIRT1	Nucleus; cytoplasm	747 aa		Deacetylase	p53, H3K9, H1K26,; H4K16, PGC1α, SREBP-1c, PPARγ NF-κB, AKT, FOXO, HIF-1α, TFAM, AceCS1, APE1, and PARP-1	Lipogenesis; Gluconeogenesis; Lipolysis; Inflammation	[31, 42, 45, 94, 123–135]
SIRT2	Cytoplasm	352 aa		Deacetylase; demyristoylase	PEPCK, α-tubulin, H4K16, and FOXO3a	Gluconeogenesis; Control of mitotic exit	[37, 136–139]
SIRT3	Mitochondria	399 aa		Deacetylase	LCAD, HMGCS2, SOD2, IDH2, PDC, and AceCS2	Lipid accumulation; Fatty acid oxidation; Ketone body production; Oxidative stress	[48, 132, 140–143]
SIRT4	Mitochondria	314 aa		ADP-ribosyltransferase; Lipoamidase	GDH, PDC	Insulin secretion	[17, 144]
SIRT5	Mitochondria	310 aa		Desuccinylase; Demalonylase; Deglutarylase	CPS1	Urea cycle	[18, 145, 146]
SIRT6	Nucleus; endoplasmic reticulum	355 aa		Depalmitoylase; ADP-ribosyltransferase Deacetylase; Demyristoylase	H3K9, H3K56, TNFα, and; PARP-1	Glucose uptake; Inflammation; DNA reparation	[16, 19, 147–150]
SIRT7	Nucleolus	400 aa		ADP-ribosyltransferase Deacetylase	PAF53, H3K18	RNA polymerase I transcription	[151, 152]

SREBP-1c: sterol regulatory element binding protein c, PGC1α: peroxisome proliferator-activated receptor gamma coactivator 1 alpha, FOXO1: Forkhead box protein O1, PPARα: peroxisome proliferator-activated receptor alpha, NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells, AKT: protein kinase B, UCP-2: uncoupling protein 2, HIF-1α: hypoxia-inducible factor 1 alpha, PPARγ: peroxisome proliferator-activated receptor gamma, TFAM: transcription factor A, mitochondrial, APE1: apurinic/apyrimidinic endonuclease 1, PARP-1: poly(ADP-ribose) polymerase 1, PEPCK: phosphoenolpyruvate carboxykinase, LCAD: long-chain acyl-CoA dehydrogenase, HMGCS2: 3-hydroxy-3-methylglutaryl-CoA synthase 2, SOD2: superoxide dismutase, IDH2: isocitrate dehydrogenase 2, PDC: pyruvate dehydrogenase complex, GDH: glutamate dehydrogenase, CPS1: carbamoyl-phosphate synthase 1, TNFα: tumor necrotic factor alpha, PAF53: RNA polymerase associated factor, and AceCS: acetyl-CoA synthetase.