The DOI matches its Crossref record; 137 of the 140 references it cites were found in a registry or an index.
Poly(ADP-ribose) signaling in cell death
Open accessAbstract
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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“parthanatos appears to occur not only as a consequence of severe/prolonged alkylating DNA damage, but also in response to oxidative stress, hypoxia, hypoglycemia, or inflammatory cues [656–658].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [657]
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Metadata
- 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
- Venue
- Molecular Aspects of Medicine
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 34
- Issue
- 6
- Pages
- 1153-1167
- ISSN
- 0098-2997 (ISSN-L)
- 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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