The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization.

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.

authors

Canet-Avilés RM,Wilson MA,Miller DW,Ahmad R,McLendon C,Bandyopadhyay S,Baptista MJ,Ringe D,Petsko GA,Cookson MR

doi

10.1073/pnas.0402959101

keywords:

subject

Has Abstract

pub_date

2004-06-15 00:00:00

pages

9103-8

issue

24

eissn

0027-8424

issn

1091-6490

pii

0402959101

journal_volume

101

pub_type

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