The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization
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- 4 June 2004
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 101 (24) , 9103-9108
- https://doi.org/10.1073/pnas.0402959101
Abstract
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.Keywords
This publication has 34 references indexed in Scilit:
- Cysteine-106 of DJ-1 is the most sensitive cysteine residue to hydrogen peroxide-mediated oxidation in vivo in human umbilical vein endothelial cellsBiochemical and Biophysical Research Communications, 2004
- Differential Effects of Parkinson's Disease-associated Mutations on Stability and Folding of DJ-1Journal of Biological Chemistry, 2004
- DJ‐1 has a role in antioxidative stress to prevent cell deathEMBO Reports, 2004
- ATP-dependent reduction of cysteine–sulphinic acid by S. cerevisiae sulphiredoxinNature, 2003
- Crystal Structure of Human DJ-1, a Protein Associated with Early Onset Parkinson's DiseaseJournal of Biological Chemistry, 2003
- The Crystal Structure of DJ-1, a Protein Related to Male Fertility and Parkinson's DiseaseJournal of Biological Chemistry, 2003
- Crystal structure of DJ‐1/RS and implication on familial Parkinson's disease 1Published by Wiley ,2003
- Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell deathHuman Molecular Genetics, 2003
- Analysis of the Cytosolic Proteome in a Cell Culture Model of Familial Amyotrophic Lateral Sclerosis Reveals Alterations to the Proteasome, Antioxidant Defenses, and Nitric Oxide Synthetic PathwaysJournal of Biological Chemistry, 2003
- [20] Processing of X-ray diffraction data collected in oscillation modePublished by Elsevier ,1997