title: DJ-1 null dopaminergic neuronal cells exhibit defects in mitochondrial function and structure: involvement of mitochondrial complex I assembly.
abstract: DJ-1 is a Parkinson's disease-associated gene whose protein product has a protective role in cellular homeostasis by removing cytosolic reactive oxygen species and maintaining mitochondrial function. However, it is not clear how DJ-1 regulates mitochondrial function and why mitochondrial dysfunction is induced by DJ-1 deficiency. In a previous study we showed that DJ-1 null dopaminergic neuronal cells exhibit defective mitochondrial respiratory chain complex I activity. In the present article we investigated the role of DJ-1 in complex I formation by using blue native-polyacrylamide gel electrophoresis and 2-dimensional gel analysis to assess native complex status. On the basis of these experiments, we concluded that DJ-1 null cells have a defect in the assembly of complex I. Concomitant with abnormal complex I formation, DJ-1 null cells show defective supercomplex formation. It is known that aberrant formation of the supercomplex impairs the flow of electrons through the channels between respiratory chain complexes, resulting in mitochondrial dysfunction. We took two approaches to study these mitochondrial defects. The first approach assessed the structural defect by using both confocal microscopy with MitoTracker staining and electron microscopy. The second approach assessed the functional defect by measuring ATP production, O(2) consumption, and mitochondrial membrane potential. Finally, we showed that the assembly defect as well as the structural and functional abnormalities in DJ-1 null cells could be reversed by adenovirus-mediated overexpression of DJ-1, demonstrating the specificity of DJ-1 on these mitochondrial properties. These mitochondrial defects induced by DJ-1mutation may be a pathological mechanism for the degeneration of dopaminergic neurons in Parkinson's disease.
authors.affiliation: Department of Biochemistry, Chungnam National University School of Medicine, Daejeon, Korea.
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Heo
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Park
authors.forename: Soung Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Kang Sik
authors.initials: KS
authors.lastname: Seo
authors.forename: Jeong Su
authors.initials: JS
authors.lastname: Han
authors.forename: Sang Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Jin Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Jong Il
authors.initials: JI
authors.lastname: Park
authors.forename: Seung Kiel
authors.initials: SK
authors.lastname: Park
authors.forename: Kyu
authors.initials: K
authors.lastname: Lim
authors.forename: Byung Doo
authors.initials: BD
authors.lastname: Hwang
authors.forename: Minho
authors.initials: M
authors.lastname: Shong
authors.forename: Gi Ryang
authors.initials: GR
authors.lastname: Kweon
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000473:pathology; D042967:Electron Transport Complex I / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D028361:Mitochondrial Diseases / Q000378:metabolism / Q000473:pathology; D015513:Oncogene Proteins / Q000172:deficiency* / Q000235:genetics*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1
chemical_list: D015513:Oncogene Proteins; D054464:Peroxiredoxins; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1; D042967:Electron Transport Complex I