Localization and functions of the human sirtuins Sirt1, Sirt2 and Sirt3. Sirt1 is found in the nucleus; it associates with several partners and targets for deacetylation, as discussed in the text. Sirt2 is found in the cytoplasm bound to the microtubule network, where it forms a complex with the histone deacetylase HDAC6. Both proteins can deacetylate α-tubulin. Sirt3 is imported into the mitochondrial matrix and proteolytically processed by the peptidase MPP, leading to its enzymatic activation (asterisk). Ac, acetyl moiety; ProteinX, an unknown protein substrate.