Table 4: Cytoplasmic sirtuins, their substrates in the cytoplasm, and their functions.

Mammalian cytoplasmic sirtuinsSubstratesFunctionsComments

SIRT1 (subcellular localization is cell type dependent)Cytoplasmic localization of SIRT1 is linked to apoptosisWhether SIRT1 enhances or decreases apoptosis and the mechanistic details remain unclear

SIRT2 (shuttles between nucleus and cytoplasm)α-tubulinMitotic exit of normal cell cycle
Regulation of mitotic checkpoint under stress
Neuronal motility and differentiation
Subcellular localization of SIRT2 modifications that modulate deacetylase activity of SIRT2, namely, phosphorylation and acetylation, is largely unspecified
Mechanism(s) through which SIRT2 regulates mitotic exit remains unclear

SIRT3
(in mitochondria)
AceCS2
GDH
ICDH2
Complex I of electron transport chain
Ku70
Nampt
MRPL10
Regulation of energy metabolism and apoptosisGDH activity is not significantly altered in Sirt3 knockout mice

SIRT4
(in mitochondria)
GDH
(SIRT4 also interacts with ANT2, SIRT3, and IDE)
Regulation of insulin secretionSIRT4 is an ADP ribosylase
No deacetylase activity is reported for SIRT4
ADP-ribosylation of ANT2, SIRT3, or IDE by SIRT4 has not been shown definitely

SIRT5
(in mitochondria)
CPS1 cytochrome c Regulation of urea cycle
Promotes apoptosis?
Exact submitochondrial localization of SIRT5, how calorie restriction alters CPS1 acetylation through SIRT5, and what lysines in CPS1 are acetylated under different nutrient availability remain controversial