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

Mammalian cytoplasmic sirtuins Substrates Functions Comments SIRT1 (subcellular localization is cell type dependent) Cytoplasmic localization of SIRT1 is linked to apoptosis Whether SIRT1 enhances or decreases apoptosis and the mechanistic details remain unclear SIRT2 (shuttles between nucleus and cytoplasm) α-tubulin Mitotic 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 apoptosis GDH activity is not significantly altered in Sirt3 knockout mice SIRT4 (in mitochondria) GDH (SIRT4 also interacts with ANT2, SIRT3, and IDE) Regulation of insulin secretion SIRT4 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