The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death
Abstract
Parkin gene mutations have been implicated in autosomal-recessive early-onset parkinsonism and lead to specific degeneration of dopaminergic neurons in midbrain. To investigate the role of Parkin in neuronal cell death, we overproduced this protein in PC12 cells in an inducible manner. In this cell line, neuronally differentiated by nerve growth factor, Parkin overproduction protected against cell death mediated by ceramide, but not by a variety of other cell death inducers (H(2)O(2), 4-hydroxynonenal, rotenone, 6-OHDA, tunicamycin, 2-mercaptoethanol and staurosporine). Protection was abrogated by the proteasome inhibitor epoxomicin and disease-causing variants, indicating that it was mediated by the E3 ubiquitin ligase activity of Parkin. Interestingly, Parkin acted by delaying mitochondrial swelling and subsequent cytochrome c release and caspase-3 activation observed in ceramide-mediated cell death. Subcellular fractionation demonstrated enrichment of Parkin in the mitochondrial fraction and its association with the outer mitochondrial membrane. Together, these results suggest that Parkin may promote the degradation of substrates localized in mitochondria and involved in the late mitochondrial phase of ceramide-mediated cell death. Loss of this function may underlie the degeneration of nigral dopaminergic neurons in patients with Parkin mutations.
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Cites
Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., et al. (1997) · Science · doi:10.1126/science.276.5321.2045 · Cited by 8,240
Greene, L. A., & Tischler, A. S. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.7.2424 · Cited by 5,553
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., & Shimizu, N. (1998) · Nature · doi:10.1038/33416 · Cited by 5,227
Basic Methods in Molecular Biology
(1986) · Elsevier eBooks · doi:10.1016/b978-0-444-01082-7.x5001-2 · Cited by 3,134
Mitochondrial control of cell death
Kroemer, G., & Reed, J. C. (2000) · Nature Medicine · doi:10.1038/74994 · Cited by 3,103
Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase
Shimura, H., Hattori, N., Kubo, S.-I., Mizuno, Y., Asakawa, S., Minoshima, S., Shimizu, N., Iwai, K., Chiba, T., Tanaka, K., et al. (2000) · Nature Genetics · doi:10.1038/77060 · Cited by 2,024 · cited 3×
“Several parkin mutations found in patients with autosomal recessive early-onset parkinsonism impair this activity (9,11).”
BackgroundProgrammed Cell Death Induced by Ceramide
Obeid, L. M., Linardic, C. M., Karolak, L. A., & Hannun, Y. A. (1993) · Science · doi:10.1126/science.8456305 · Cited by 1,794
The ubiquitin pathway in Parkinson's disease
Leroy, E., Boyer, R., Auburger, G., Leube, B., Ulm, G., Mezey, E., Harta, G., Brownstein, M. J., Jonnalagada, S., Chernova, T., et al. (1998) · Nature · doi:10.1038/26652 · Cited by 1,571
Association between Early-Onset Parkinson's Disease and Mutations in the Parkin Gene
Lücking, C. B., Dürr, A., Bonifati, V., Vaughan, J., De Michele, G., Gasser, T., Harhangi, B. S., Meco, G., Denèfle, P., Wood, N. W., et al. (2000) · New England Journal of Medicine · doi:10.1056/nejm200005253422103 · Cited by 1,433
Joazeiro, C. A. P., & Weissman, A. M. (2000) · Cell · doi:10.1016/s0092-8674(00)00077-5 · Cited by 1,249
Cited by
Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455
Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
Narendra, D., Tanaka, A., Suen, D.-F., & Youle, R. J. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200809125 · Cited by 4,026
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
PINK1-dependent recruitment of Parkin to mitochondria in mitophagy
Vives-Bauza, C., Zhou, C., Huang, Y., Cui, M., de Vries, R. L. A., Kim, J., May, J., Tocilescu, M. A., Liu, W., Ko, H. S., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911187107 · Cited by 1,616
Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity
West, A. B., Moore, D. J., Biskup, S., Bugayenko, A., Smith, W. W., Ross, C. A., Dawson, V. L., & Dawson, T. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507360102 · Cited by 1,228
Metadata
- Authors
- Darios, F.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-03-01
- Volume
- 12
- Issue
- 5
- Pages
- 517-526
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2129248872
- Cited by
- 403
- References
- 40
- FWCI
- 18.22
- Type
- journal article
- Language
- en
- Open access
- closed
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