The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization
| Autor: | Rili Ahmad, Dagmar Ringe, Mark R. Cookson, Mark A. Wilson, Melisa J. Baptista, Gregory A. Petsko, Sourav Bandyopadhyay, David Miller, Chris McLendon, Rosa M. Canet-Avilés |
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| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Gene isoform
Models Molecular 1-Methyl-4-phenylpyridinium Protein Deglycase DJ-1 Static Electricity Biology Mitochondrion medicine.disease_cause Transfection Neuroprotection chemistry.chemical_compound Cell Line Tumor medicine Humans Protein Isoforms Cysteine Oncogene Proteins Neurotransmitter Agents Multidisciplinary PARK7 Intracellular Signaling Peptides and Proteins Intracellular Membranes Biological Sciences Recombinant Proteins Cell biology Mitochondria Oxidative Stress Neuroprotective Agents Biochemistry chemistry Amino Acid Substitution Cysteine sulfinic acid Oxidation-Reduction Oxidative stress |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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