The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Apoptosis-inducing factor is involved in the regulation of caspase-independent neuronal cell death
Open accessAbstract
Caspase-independent death mechanisms have been shown to execute apoptosis in many types of neuronal injury. P53 has been identified as a key regulator of neuronal cell death after acute injury such as DNA damage, ischemia, and excitotoxicity. Here, we demonstrate that p53 can induce neuronal cell death via a caspase-mediated process activated by apoptotic activating factor-1 (Apaf1) and via a delayed onset caspase-independent mechanism. In contrast to wild-type cells, Apaf1-deficient neurons exhibit delayed DNA fragmentation and only peripheral chromatin condensation. More importantly, we demonstrate that apoptosis-inducing factor (AIF) is an important factor involved in the regulation of this caspase-independent neuronal cell death. Immunofluorescence studies demonstrate that AIF is released from the mitochondria by a mechanism distinct from that of cytochrome-c in neurons undergoing p53-mediated cell death. The Bcl-2 family regulates this release of AIF and subsequent caspase-independent cell death. In addition, we show that enforced expression of AIF can induce neuronal cell death in a Bax- and caspase-independent manner. Microinjection of neutralizing antibodies against AIF significantly decreased injury-induced neuronal cell death in Apaf1-deficient neurons, indicating its importance in caspase-independent apoptosis. Taken together, our results suggest that AIF may be an important therapeutic target for the treatment of neuronal injury.
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Cites
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The Bcl-2 Protein Family: Arbiters of Cell Survival
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Molecular characterization of mitochondrial apoptosis-inducing factor
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Self-citationBCL-2 family members and the mitochondria in apoptosis
Gross, A., McDonnell, J. M., & Korsmeyer, S. J. (1999) · Genes & Development · doi:10.1101/gad.13.15.1899 · Cited by 3,641
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Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice
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Endonuclease G is an apoptotic DNase when released from mitochondria
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Reduced Apoptosis and Cytochrome c–Mediated Caspase Activation in Mice Lacking Caspase 9
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X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death
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Bcl-xL Regulates the Membrane Potential and Volume Homeostasis of Mitochondria
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Cited by
Mitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598
Self-citationInhibition of Macroautophagy Triggers Apoptosis
Boya, P., González-Polo, R.-A., Casares, N., Perfettini, J.-L., Dessen, P., Larochette, N., Métivier, D., Meley, D., Souquere, S., Yoshimori, T., et al. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.3.1025-1040.2005 · Cited by 1,625
Self-citationCrosstalk between apoptosis.; necrosis and autophagy
Nikoletopoulou, V., Markaki, M., Palikaras, K., & Tavernarakis, N. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.06.001 · Cited by 1,366
“Chemical inhibition or genetic ablation of PARP1, as well as of AIF prevent DNA-damage-induced death, [73,74,80] further demonstrating the absolute requirement of PARP1 and AIF in necroptosis.”
BackgroundApoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death
Yu, S.-W., Andrabi, S. A., Wang, H., Kim, N. S., Poirier, G. G., Dawson, T. M., & Dawson, V. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606528103 · Cited by 718
Self-citationMolecular targets in cerebral ischemia for developing novel therapeutics
Mehta, S. L., Manhas, N., & Raghubir, R. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2006.11.003 · Cited by 708
Metadata
- Authors
- Cregan, S. P., Fortin, A., MacLaurin, J. G., Callaghan, S. M., Cecconi, F., Yu, S.-W., Dawson, T. M., Dawson, V. L., Park, D. S., Kroemer, G., & Slack, R. S.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2002-07-29
- Volume
- 158
- Issue
- 3
- Pages
- 507-517
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2134738066
- Cited by
- 477
- References
- 60
- FWCI
- 11.77
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Cregan, S. P., Fortin, A., MacLaurin, J. G., Callaghan, S. M., Cecconi, F., Yu, S.-W., Dawson, T. M., Dawson, V. L., Park, D. S., Kroemer, G., & Slack, R. S. (2002). Apoptosis-inducing factor is involved in the regulation of caspase-independent neuronal cell death. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200202130
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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