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Mol Aspects Med. 2013 Dec;34(6):1168-201. doi: 10.1016/j.mam.2013.01.004. Epub 2013 Jan 25.

Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes.

Author information

1
Nestlé Institute of Health Sciences, Lausanne CH-1015, Switzerland.

Abstract

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.

KEYWORDS:

Metabolism; Mitochondria; NAD(+); Oxidative stress; Poly(ADP-ribose) polymerase; Sirtuins SIRT1

PMID:
23357756
PMCID:
PMC3676863
DOI:
10.1016/j.mam.2013.01.004
[Indexed for MEDLINE]
Free PMC Article

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