Table 1.

Biological functions of sirtuin proteins related to energy metabolism.

Protein	Location	Enzyme activity	Biological functions related to energy metabolism
SIRT1	Nucleus	Deacetylase	♦SIRT1 controls gluconeogenesis and glycolysis in the liver by activating PGC-1, but does not regulate the effect of PGC-1 on mitochondrial genes56. ♦SIRT1 inhibits PPAR-γ activity, which in turn promotes fat mobilization in white adipose tissue when calorie intake is reduced57. ♦SIRT1 inhibits the expression of uncoupling protein 2 gene and regulates insulin secretion of islet B cells58.
SIRT2	Cytoplasm Nucleus	Deacetylase	♦SIRT2 promotes deacetylated hepatocyte nuclear factor (FOXO1) to bind to PPARγ, thereby inhibiting PPARγ activity and promoting adipocyte differentiation59. ♦SIRT2 deacetylates phosphoenolpyruvate carboxykinase, FOXO1, and PGC-1α. Then it regulates gluconeogenesis through a variety of pathways60.
SIRT3	Mitochondria	Deacetylase	♦SIRT3 regulates the metabolic transition between mitochondrial respiration and glycolysis in endothelial cells61. ♦SIRT3 activation attenuates the damage caused by ROS through superoxide dismutase 2 and hypoxia-inducible factor-1α (HIF-1α) regulated pathways53. ♦An increase in SIRT3 activity restores complex I activity and ATP levels in the mitochondrial electron transport chain62.
SIRT4	Mitochondria	ADP-ribosyltransferase	♦SIRT4 regulates insulin secretion by inhibiting glutamate dehydrogenase activity in the mitochondrial matrix63. ♦SIRT4 inhibits malonyl-CoA decarboxylase activity in mitochondria via deacetylation, thereby increasing malonyl CoA and regulating fatty acid oxidation64. ♦SIRT4 inhibits pyruvate dehydrogenase activity, which affects glycolysis and TCA cycle65.
SIRT5	Mitochondria	Deacetylase	♦SIRT5 regulates glycolysis, β-oxidation of fatty acids, TCA cycle and electron transport chain52. ♦Denucleated SIRT5 regulates the activity of 3-hydroxy-3-methylglutaryl-COA synthetase 2 to regulate ketone body formation66.
SIRT6	Nucleus	Deacetylase/ADP-ribosyltransferase	♦SIRT6 affects glucose metabolism by inhibiting the expression of HIF-1α and other glycolytic genes67. ♦SIRT6 acetylates PGC-1α by modifying the activity of acetyltransferase general control non-depressible 5, and indirectly controls hepatic glycogenogenesis68. ♦SIRT6 negatively regulates triacylglycerol synthesis, thereby participating in lipid metabolism69.
SIRT7	Nucleolus	Deacetylase	♦SIRT7 deacetylates the lysine on the (GABP) subunit β1 and promotes the formation and transcriptional activation of α and GA-binding protein β heterotetramers, thereby regulating the expression of nuclear-encoded mitochondrial genes and maintaining mitochondrial steady state47.