Figure 1.

Mammalian sirtuins: general functions and activation in response to stress (a) Schematic representation of the main enzymatic activities of mammalian sirtuins. Sirtuins catalyze deacetylation of protein targets by transferring the acetyl group to NAD+, concomitant with the release of nicotinamide (NAM) and 2′-O-acetyl-ADP-ribose (upper panel). In the mono-ADP-ribosylation reaction, the ADP-ribose (ADPR) is transferred from NAD⁺ to the substrate, leading to release of NAM (lower panel). NAM is a potent inhibitor of the enzymatic activity of sirtuins. (b) Schematic representation of the structure and subcellular distribution of mammalian sirtuins. SIRT7 nuclear and nucleolar localization sequences (NLS and NoLS, respectively) are indicated. (c) Scheme depicting the mechanisms involved in sirtuins activation following stress (red) and their main biological functions (green).