title: [Function of DJ-1 in mitochondria].
abstract: Parkinson's disease is a degenerative disorder of the central nervous system caused by selective dopamine-generating cell death, and oxidative stress and mitochondrial dysfunction are thought to be responsible for the onset of Parkinson's disease. While most cases of Parkinson's disease are idiopathic, 5-10% of cases are attributed to genetic factors. DJ-1 was first identified as an activated ras-dependent oncogene and later found to be a causative gene for a familial form of Parkinson's disease, PARK7. We and others found that DJ-1 plays roles in transcriptional regulation and anti-oxidative stress function, and loss of its function is thought to affect the onset of Parkinson's disease. DJ-1 is mainly located in the cytoplasma and nucleus and partially in mitochondria. When mice or mouse cells were treated with bisphenol A, an endocrine disruptor and inducer of reactive oxygen species, DJ-1 was translocated into mitochondria to maintain mitochondrial complex I activity. We also found that DJ-1 directly bound to and was co-localized with NDUFA4 and ND1, nuclear and mitochondrial DNA-encoding subunits of mitochondrial complex I, respectively, and that these associations were enhanced by oxidative stress. Furthermore, complex I activity was reduced in two types of DJ-1-knockdown NIH3T3 and HEK293 cells. These findings suggest that DJ-1 is an integral mitochondrial protein and maintains mitochondrial complex I activity to regulate mitochondrial homeostasis.
authors.affiliation: Hokkaido University Graduate School of Pharmaceutical Science, Kita-ku, Sapporo, Japan. nkazu@pharm.hokudai.ac.jp
authors.forename: Kazuko
authors.initials: K
authors.lastname: Takahashi-Niki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Niki
authors.forename: Sanae
authors.initials: S
authors.lastname: Iguchi-Ariga
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ariga
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology; D006706:Homeostasis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000502:physiology*; D015513:Oncogene Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D010300:Parkinson Disease / Q000503:physiopathology; D010636:Phenols / Q000494:pharmacology; D000071617:Protein Deglycase DJ-1; D051381:Rats; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D010636:Phenols; D000071617:Protein Deglycase DJ-1; C105131:PARK7 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds