Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes.
Poly(ADP-ribose) polymerases (PARPs) are NAD(+) dependent enzymes that were identified as DNA repair proteins, however, today it seems clear that PARPs are responsible for a plethora of biological functions. Sirtuins (SIRTs) are NAD(+)-dependent deacetylase enzymes involved in the same biological processes as PARPs raising the question whether PARP and SIRT enzymes may interact with each other in physiological and pathophysiological conditions. Hereby we review the current understanding of the SIRT-PARP interplay in regard to the biochemical nature of the interaction (competition for the common NAD(+) substrate, mutual posttranslational modifications and direct transcriptional effects) and the physiological or pathophysiological consequences of the interactions (metabolic events, oxidative stress response, genomic stability and aging). Finally, we give an overview of the possibilities of pharmacological intervention to modulate PARP and SIRT enzymes either directly, or through modulating NAD(+) homeostasis.
Nestlé Institute of Health Sciences, Lausanne CH-1015, Switzerland.
Carles
C
Cantó
Anthony A
AA
Sauve
Peter
P
Bai
D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D009243:NAD / Q000096:biosynthesis / Q000378:metabolism*; D018384:Oxidative Stress; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009243:NAD; D011065:Poly(ADP-ribose) Polymerases; D037761:Sirtuins
Metabolism; Mitochondria; NAD(+); Oxidative stress; Poly(ADP-ribose) polymerase; Sirtuins SIRT1