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

Overview

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.

publication date

  • June 4, 2004

Research

keywords

  • Cysteine
  • Mitochondria
  • Neuroprotective Agents
  • Oncogene Proteins

Identity

PubMed Central ID

  • PMC428480

Scopus Document Identifier

  • 2942684871

Digital Object Identifier (DOI)

  • 10.1073/pnas.0402959101

PubMed ID

  • 15181200

Additional Document Info

volume

  • 101

issue

  • 24