The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization
Open accessAbstract
Loss-of-function DJ-1 mutations can cause early-onset Parkinson's disease. The function of DJ-1 is unknown, but an acidic isoform accumulates after oxidative stress, leading to the suggestion that DJ-1 is protective under these conditions. We addressed whether this represents a posttranslational modification at cysteine residues by systematically mutating cysteine residues in human DJ-1. WT or C53A DJ-1 was readily oxidized in cultured cells, generating a pI 5.8 isoform, but an artificial C106A mutant was not. We observed a cysteine-sulfinic acid at C106 in crystalline DJ-1 but no modification of C53 or C46. Oxidation of DJ-1 was promoted by the crystallization procedure. In addition, oxidation-induced mitochondrial relocalization of DJ-1 and protection against cell death were abrogated in C106A but not C53A or C46A. We suggest that DJ-1 protects against neuronal death, and that this is signaled by acidification of the key cysteine residue, C106.
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Cited by
Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
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The Role of Oxidative Stress in Parkinson's Disease
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Inflammation and immune dysfunction in Parkinson disease
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Redox metabolism: ROS as specific molecular regulators of cell signaling and function
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Metadata
- Authors
- Canet-Avilés, R. M., Wilson, M. A., Miller, D. W., Ahmad, R., McLendon, C., Bandyopadhyay, S., Baptista, M. J., Ringe, D., Petsko, G. A., & Cookson, M. R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-06-04
- Volume
- 101
- Issue
- 24
- Pages
- 9103-9108
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2171873547
- Cited by
- 1,116
- References
- 32
- FWCI
- 35.65
- Type
- journal article
- Language
- en
- Open access
- green
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- Canet-Avilés, R. M., Wilson, M. A., Miller, D. W., Ahmad, R., McLendon, C., Bandyopadhyay, S., Baptista, M. J., Ringe, D., Petsko, G. A., & Cookson, M. R. (2004). The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0402959101
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