Cited by 276Cell death mechanisms and regulationPARP inhibition in cancer therapySirtuins and Resveratrol in Medicine

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Poly(ADP-ribose) signaling in cell death

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Virág, László, Robaszkiewicz, Agnieszka, Rodriguez-Vargas, Jose Manuel, Oliver, Francisco Javier·2013·Molecular Aspects of Medicine

DOI 10.1016/j.mam.2013.01.007

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Abstract

Poly(ADP-ribosyl)ation (PARylation) is a reversible protein modification carried out by the concerted actions of poly(ADP-ribose) polymerase (PARP) enzymes and poly(ADP-ribose) (PAR) decomposing enzymes such as PAR glycohydrolase (PARG) and ADP-ribosyl hydrolase 3 (ARH3). Reversible PARylation is a pleiotropic regulator of various cellular functions but uncontrolled PARP activation may also lead to cell death. The cellular demise pathway mediated by PARylation in oxidatively stressed cells has been described almost thirty years ago. However, the underlying molecular mechanisms have only begun to emerge relatively recently. PARylation has been implicated in necroptosis, autophagic cell death but its role in extrinsic and intrinsic apoptosis appears to be less predominant and depends largely on the cellular model used. Currently, three major pathways have been made responsible for PARP-mediated necroptotic cell death: (1) compromised cellular energetics mainly due to depletion of NAD, the substrate of PARPs; (2) PAR mediated translocation of apoptosis inducing factor (AIF) from mitochondria to nucleus (parthanatos) and (3) a mostly elusive crosstalk between PARylation and cell death/survival kinases and phosphatases. Here we review how these PARP-mediated necroptotic pathways are intertwined, how PARylation may contribute to extrinsic and intrinsic apoptosis and discuss recent developments on the role of PARylation in autophagy and autophagic cell death.

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Authors: Virág, L., Robaszkiewicz, A., Rodriguez-Vargas, J. M., & Oliver, F. J.
Affiliations: University of Debrecen (HU)
Instituto de Parasitología y Biomedicina "López - Neyra" (ES)
Corresponding author: Virág, László
Oliver, Francisco Javier
ORCID: Virág, László
Robaszkiewicz, Agnieszka
Oliver, Francisco Javier
Venue: Molecular Aspects of Medicine
Publisher: Elsevier BV
Published: 2013-12
Volume: 34
Issue: 6
Pages: 1153-1167
ISSN: 0098-2997 (ISSN-L)
DOI: 10.1016/j.mam.2013.01.007
OpenAlex: W2076542944
Cited by: 273
References: 140
Citations by year: 2026: 8 · 2025: 20 · 2024: 15 · 2023: 17 · 2022: 23 · 2021: 21 · 2020: 21 · 2019: 20 · 2018: 14 · 2017: 23 · 2016: 29 · 2015: 26 · 2014: 22 · 2013: 13
FWCI: 2.85
Type: journal article
Language: en
Open access: green
doi.org
Licence: cc-by-nc-nd
Locations: Molecular Aspects of Medicine (publishedVersion)
PubMed (publishedVersion)
Institutional Repository of the University of Granada (University of Granada) (submittedVersion, cc-by-nc-nd)
University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion, cc-by-nc-nd)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Keywords: poly(ADP-ribose) polymerase, necroptosis, parthanatos, apoptosis, autophagic cell death, NAD+ depletion, apoptosis-inducing factor, oxidative stress, cell death signaling
MeSH terms: Animals, Gene Expression Regulation, Humans, Mitochondria, Poly Adenosine Diphosphate Ribose, Poly(ADP-ribose) Polymerases, Protein Binding, Protein Processing, Post-Translational, Signal Transduction, Cell Death, Gene Regulatory Networks

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Poly(ADP-ribose) signaling in cell death

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