Nuclear and mitochondrial conversations in cell death: PARP-1 and AIF signaling
Abstract
Different cell-death mechanisms control many physiological and pathological processes in humans. Mitochondria play important roles in cell death through the release of pro-apoptotic factors such as cytochrome c and apoptosis-inducing factor (AIF), which activate caspase-dependent and caspase-independent cell death, respectively. Poly(ADP-ribose) polymerase 1 (PARP-1) is emerging as an important activator of caspase-independent cell death. PARP-1 generates the majority of long, branched poly(ADP-ribose) (PAR) polymers following DNA damage. Overactivation of PARP-1 initiates a nuclear signal that propagates to mitochondria and triggers the release of AIF. AIF then shuttles from mitochondria to the nucleus and induces peripheral chromatin condensation, large-scale fragmentation of DNA and, ultimately, cytotoxicity. Identification of the pro-death and pro-survival signals in the PARP-1-mediated cell-death program might provide novel therapeutic targets in human diseases.
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Even slower, sustained calcium influx through calcium-permeable AMPA receptors can be damaging through neuronal nitric oxide synthase activation, nitric oxide generation, and PARP-1 activation.
“Even slower, consistent Ca 2+ influx through Ca 2+ -permeable AMPA receptors can be damaging via activation of neuronal nitric oxide synthase and generation of nitric oxide and resultant activation of Poly(ADP-ribose) polymerase 1 (PARP-1), (Fig. 1b), [109, 110].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [110]
PARP-1 causes release of apoptosis-inducing factor through a nuclear signal that reaches mitochondria.
“PARP-1 leads to the release of apoptosis-inducing factor (AIF) via a nuclear signal that proliferates to mitochondria [110].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [110]
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- Authors
- Hong, S. J., Dawson, T. M., & Dawson, V. L.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Dawson, Valina L.
- Venue
- Trends in Pharmacological Sciences
- Publisher
- Elsevier BV
- Published
- 2004-05
- Volume
- 25
- Issue
- 5
- Pages
- 259-264
- ISSN
- 0165-6147 (ISSN-L)
- OpenAlex
- W1968458167
- Cited by
- 463
- References
- 57
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 17 · 2023: 10 · 2022: 11 · 2021: 12 · 2020: 17 · 2019: 18 · 2018: 20 · 2017: 21 · 2016: 11 · 2015: 14 · 2014: 25 · 2013: 20 · 2012: 26
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Pharmacological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Johns Hopkins University
- National Institutes of Health
- Robert Packard Center for ALS Research, Johns Hopkins University
- 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
- PARP1, apoptosis-inducing factor, mitochondrial release, caspase-independent cell death, poly(ADP-ribose), DNA damage, chromatin condensation, DNA fragmentation, cell death
- MeSH terms
- Flavoproteins, Humans, Membrane Proteins, Mitochondria, Poly(ADP-ribose) Polymerases, Cell Death, Caspases, Apoptosis Inducing Factor
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