Metabolic roles of poly(ADP-ribose) polymerases

Abstract

Poly(ADP-ribosyl)ation (PARylation) is an evolutionarily conserved reaction that had been associated with numerous cellular processes such as DNA repair, protein turnover, inflammatory regulation, aging or metabolic regulation. The metabolic regulatory tasks of poly(ADP-ribose) polymerases (PARPs) are complex, it is based on the regulation of metabolic transcription factors (e.g. SIRT1, nuclear receptors, SREBPs) and certain cellular energy sensors. PARP over-activation can cause damage to mitochondrial terminal oxidation, while the inhibition of PARP-1 or PARP-2 can induce mitochondrial oxidation by enhancing the mitotropic tone of gene transcription and signal transduction. These PARP-mediated processes impact on higher order metabolic regulation that modulates lipid metabolism, circadian oscillations and insulin secretion and signaling. PARP-1, PARP-2 and PARP-7 are related to metabolic diseases such as diabetes, alcoholic and non-alcoholic fatty liver disease (AFLD, NAFLD), or on a broader perspective to Warburg metabolism in cancer or the metabolic diseases accompanying aging.

Novel serum metabolomics‐based approach by gas chromatography/triple quadrupole mass spectrometry for detection of human skin cancers: Candidate biomarkers

“…34 The roles of PARP in carcinogenesis are complex; overactivation of PARP can cause damage to mitochondrial terminal oxidation, whereas PARP inhibition can induce mitochondrial oxidation. 34 Although the mechanism by which ribose levels are decreased is unclear, this alteration might be significant as a biomarker. Abaffy et al identified increased levels of lauric acid and palmitic acid by metabolomics using skin tissue from patients with melanoma; 28 however, lauric acid showed no remarkable changes, and palmitic acid was not analyzed in the present study.…”

ADP‐ribosylation: new facets of an ancient modification

“…ADP‐ribosylation in mammals is known to regulate a number of different processes . Best understood is regulation of DNA‐damage repair pathways by PARP1‐3 that are activated upon binding to DNA breaks PARP1 also plays roles in transcription and metabolism . The functions of other PARPs are comparatively much less understood .…”

“…Several PARPs (PARP7 PARP10, PARP12 and PARP13) are involved in mechanisms of post‐transcriptional regulation of mRNA, mediated either by RNA‐binding domains or by ADP‐ribosylation of RNA‐binding proteins . In addition, PARP10 has been implied in the regulation of NF‐kB , GSK3β and transcription . Also, PARP9 and PARP14 are suggested to act on transcription, in particular of genes required for macrophage activation .…”

DNA damage response upon environmental contaminants: An exhausting work for genomic integrity

“…PARP-1 also regulates metabolism by interacting with different metabolic partners: SIRT1 (sirtuin 1), nuclear factors and energy sensors (AMPK) [4], showing the possible dialogues between DNA damage and metabolic checkpoints.…”