The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila
Open accessAbstract
Mutations in PTEN-induced kinase 1 ( pink1 ) or parkin cause autosomal-recessive and some sporadic forms of Parkinson's disease. pink1 acts upstream of parkin in a common genetic pathway to regulate mitochondrial integrity in Drosophila . Mitochondrial morphology is maintained by a dynamic balance between the opposing actions of mitochondrial fusion, controlled by Mitofusin ( mfn ) and Optic atrophy 1 ( opa1 ), and mitochondrial fission, controlled by drp1 . Here, we explore interactions between pink1 / parkin and the mitochondrial fusion/fission machinery. Muscle-specific knockdown of the fly homologue of Mfn ( Marf ) or opa1 , or overexpression of drp1 , results in significant mitochondrial fragmentation. Mfn -knockdown flies also display altered cristae morphology. Interestingly, knockdown of Mfn or opa1 or overexpression of drp1 , rescues the phenotypes of muscle degeneration, cell death, and mitochondrial abnormalities in pink1 or parkin mutants. In the male germline, we also observe genetic interactions between pink1 and the testes-specific mfn homologue fuzzy onion , and between pink1 and drp1 . Our data suggest that the pink1 / parkin pathway promotes mitochondrial fission and/or inhibits fusion by negatively regulating mfn and opa1 function, and/or positively regulating drp1 . However, pink1 and parkin mutant flies show distinct mitochondrial phenotypes from drp1 mutant flies, and flies carrying a heterozygous mutation in drp1 enhance the pink1 -null phenotype, resulting in lethality. These results suggest that pink1 and parkin are likely not core components of the drp1 -mediated mitochondrial fission machinery. Modification of fusion and fission may represent a novel therapeutic strategy for Parkinson's disease.
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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
Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1
Valente, E. M., Abou-Sleiman, P. M., Caputo, V., Muqit, M. M. K., Harvey, K., Gispert, S., Ali, Z., Del Turco, D., Bentivoglio, A. R., Healy, D. G., et al. (2004) · Science · doi:10.1126/science.1096284 · Cited by 3,481
Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin
Clark, I. E., Dodson, M. W., Jiang, C., Cao, J. H., Huh, J. R., Seol, J. H., Yoo, S. J., Hay, B. A., & Guo, M. (2006) · Nature · doi:10.1038/nature04779 · Cited by 1,788
Self-citationThe Role of Dynamin-Related Protein 1, a Mediator of Mitochondrial Fission, in Apoptosis
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Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin
Park, J., Lee, S. B., Lee, S., Kim, Y., Song, S., Kim, S., Bae, E., Kim, J., Shong, M., Kim, J.-M., et al. (2006) · Nature · doi:10.1038/nature04788 · Cited by 1,705
Functions and dysfunctions of mitochondrial dynamics
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Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants
Greene, J. C., Whitworth, A. J., Kuo, I., Andrews, L. A., Feany, M. B., & Pallanck, L. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0737556100 · Cited by 1,203
The PINK1/Parkin pathway regulates mitochondrial morphology
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Cited by
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
Mitochondria: In Sickness and in Health
Nunnari, J., & Suomalainen, A. (2012) · Cell · doi:10.1016/j.cell.2012.02.035 · Cited by 3,479
Youle, R. J., & Narendra, D. P. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3028 · Cited by 3,273
The Roles of PINK1, Parkin, and Mitochondrial Fidelity in Parkinson’s Disease
Pickrell, A. M., & Youle, R. J. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.007 · Cited by 2,310
Mitochondrial fusion and fission in cell life and death
Westermann, B. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3013 · Cited by 2,002
Metadata
- Authors
- Deng, H., Dodson, M. W., Huang, H., & Guo, M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2008-09-23
- Volume
- 105
- Issue
- 38
- Pages
- 14503-14508
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1976645698
- Cited by
- 689
- References
- 12
- FWCI
- 23.82
- Type
- journal article
- Language
- en
- Open access
- green
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