The taming of PARP1 and its impact on NAD+ metabolism

• Published in: Molecular metabolism (Germany) Vol. 38; p. 100950
• Main Authors: Hurtado-Bagès, Sarah, Knobloch, Gunnar, Ladurner, Andreas G., Buschbeck, Marcus
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.08.2020; Elsevier
• Subjects: Epigenetics; Homeostasis; MacroH2A; Metabolism; NAD; PARP1; Review; NAD; Epigenetics; Homeostasis; MacroH2A; PARP1; Metabolism
• ISSN: 2212-8778; 2212-8778
• DOI: 10.1016/j.molmet.2020.01.014

Poly-ADP-ribose polymerases (PARPs) are key mediators of cellular stress response. They are intimately linked to cellular metabolism through the consumption of NAD+. PARP1/ARTD1 in the nucleus is the major NAD+ consuming activity and plays a key role in maintaining genomic integrity. In this review, we discuss how different organelles are linked through NAD+ metabolism and how PARP1 activation in the nucleus can impact the function of distant organelles. We discuss how differentiated cells tame PARP1 function by upregulating an endogenous inhibitor, the histone variant macroH2A1.1. The presence of macroH2A1.1, particularly in differentiated cells, raises the threshold for the activation of PARP1 with consequences for DNA repair, gene transcription, and NAD+ homeostasis. •Beyond DNA repair, PARP1 is essential for metabolic homeostasis.•Epigenetic mechanisms prevent metabolic disorders through PARP1 taming.•Beyond cancer, the development of PARP1 inhibitors offers diverse clinical potential.