DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase

Eva Andres-Mateos, Celine Perier, Li Zhang, Beatrice Blanchard-Fillion, Todd M. Greco, Bobby Thomas, Seok Ko Han, Masayuki Sasaki, Harry Ischiropoulos, Serge Przedborski, Ted M. Dawson, Valina L. Dawson

Research output: Contribution to journalArticlepeer-review

410 Scopus citations


Parkinson's disease (PD) is a common neurodegenerative movement disorder. Whereas the majority of PD cases are sporadic, rare genetic defects have been linked to this prevalent movement disorder. Mutations in DJ-1 are associated with autosomal recessive early-onset PD. The exact biochemical function of DJ-1 has remained elusive. Here we report the generation of DJ-1 knockout (KO) mice by targeted deletion of exon 2 and exon 3. There is no observable degeneration of the central dopaminergic pathways, and the mice are anatomically and behaviorally similar to WT mice. Fluorescent Amplex red measurements of H 2O2 indicate that isolated mitochondria from young and old DJ-1 KO mice have a 2-fold increase in H2O2. DJ-1 KO mice of 2-3 months of age have a 60% reduction in mitochondrial aconitase activity without compromising other mitochondrial processes. At an early age there are no differences in antioxidant enzymes, but in older mice there is an up-regulation of mitochondrial manganese superoxide dismutase and glutathione peroxidase and a 2-fold increase in mitochondrial glutathione peroxidase activity. Mutational analysis and mass spectrometry reveal that DJ-1 is an atypical peroxiredoxin-like peroxidase that scavenges H2O2 through oxidation of Cys-106. In vivo there is an increase of DJ-1 oxidized at Cys-106 after 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine intoxication of WT mice. Taken together these data indicate that the DJ-1 KO mice have a deficit in scavenging mitochondrial H2O2 due to the physiological function of DJ-1 as an atypical peroxiredoxin-like peroxidase.

Original languageEnglish (US)
Pages (from-to)14807-14812
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number37
StatePublished - Sep 11 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General


  • Glutathione peroxidase
  • Manganese superoxide dismutase
  • Mitochondria
  • PARK7
  • Parkinson's disease


Dive into the research topics of 'DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase'. Together they form a unique fingerprint.

Cite this