Parthanatos: mitochondrial‐linked mechanisms and therapeutic opportunities
Open accessAbstract
Cells die by a variety of mechanisms. Terminally differentiated cells such as neurones die in a variety of disorders, in part, via parthanatos, a process dependent on the activity of poly (ADP‐ribose)‐polymerase (PARP). Parthanatos does not require the mediation of caspases for its execution, but is clearly mechanistically dependent on the nuclear translocation of the mitochondrial‐associated apoptosis‐inducing factor (AIF). The nuclear translocation of this otherwise beneficial mitochondrial protein, occasioned by poly (ADP‐ribose) (PAR) produced through PARP overactivation, causes large‐scale DNA fragmentation and chromatin condensation, leading to cell death. This review describes the multistep course of parthanatos and its dependence on PAR signalling and nuclear AIF translocation. The review also discusses potential targets in the parthanatos cascade as promising avenues for the development of novel, disease‐modifying, therapeutic agents. Linked Articles: This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue‐8
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Parthanatos occurs not only as a consequence of severe/prolonged alkylating DNA damage, but also in response to oxidative stress, hypoxia, hypoglycemia, or inflammatory cues.
“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 [656]
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- Authors
- Fatokun, A. A., Dawson, V. L., & Dawson, T. M.
- Affiliations
- University of Nottingham (GB)
- Johns Hopkins University (US)
- Corresponding author
- Fatokun, Amos A
- Dawson, Ted M
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2014-03-28
- Volume
- 171
- Issue
- 8
- Pages
- 2000-2016
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC3976618
- OpenAlex
- W2117049355
- Cited by
- 594
- References
- 184
- Citations by year
- 2026: 44 · 2025: 57 · 2024: 47 · 2023: 67 · 2022: 67 · 2021: 56 · 2020: 68 · 2019: 46 · 2018: 42 · 2017: 37 · 2016: 37 · 2015: 14 · 2014: 12
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (P50DA000266, DA000266)
- National Institute of Neurological Disorders and Stroke (NS 38377, NS067525, R37NS067525, P50NS038377, R01NS067525)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- parthanatos, apoptosis, poly(ADP-ribose) polymerase, apoptosis-inducing factor, poly(ADP-ribose), DNA fragmentation, chromatin condensation, neurodegeneration, disease-modifying therapy
- MeSH terms
- Poly (ADP-Ribose) Polymerase-1, Animals, Cell Survival, Glycoside Hydrolases, Humans, Mitochondria, Models, Biological, Poly Adenosine Diphosphate Ribose, Poly(ADP-ribose) Polymerases, Cell Death, Neurodegenerative Diseases, Active Transport, Cell Nucleus, Apoptosis Inducing Factor, Molecular Targeted Therapy
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