title: Biochemical analysis of cybrids expressing mitochondrial DNA from Contursi kindred Parkinson's subjects.
abstract: Complex I activity is reduced in cytoplasmic hybrid (cybrid) cell lines that contain mitochondrial DNA (mtDNA) from sporadic Parkinson's disease (PD) patients. This implies that mtDNA aberration occurs in sporadic PD. To assess the integrity of mtDNA in autosomal dominant PD arising from mutation of the alpha-synuclein gene, we transferred mitochondrial genes from PD-affected members of the Italian-American Contursi kindred to cells previously depleted of their endogenous mtDNA. Unlike cybrid cell lines expressing mtDNA from persons with sporadic or maternally inherited PD, the resultant Contursi cybrid lines did not manifest complex I deficiency, indicating that in Contursi PD mtDNA integrity is relatively preserved. Compared to control cybrids, however, Contursi cybrid lines did show some evidence of oxidative stress. For reasons that are unclear, at least a limited amount of mtDNA damage may nevertheless develop in PD patients with alpha-synuclein mutation.
authors.affiliation: Center for the Study of Neurodegenerative Diseases, University of Virginia Health System, Charlottesville, Virginia, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Swerdlow
authors.forename: J K
authors.initials: JK
authors.lastname: Parks
authors.forename: D S
authors.initials: DS
authors.lastname: Cassarino
authors.forename: D R
authors.initials: DR
authors.lastname: Binder
authors.forename: J P
authors.initials: JP
authors.lastname: Bennett
authors.forename: G
authors.initials: G
authors.lastname: Di Iorio
authors.forename: L I
authors.initials: LI
authors.lastname: Golbe
authors.forename: W D
authors.initials: WD
authors.lastname: Parker
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D002374:Catalase / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000097:blood / Q000235:genetics*; D004579:Electron Transport; D042967:Electron Transport Complex I; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D005260:Female; D005799:Genes, Dominant; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D006822:Hybrid Cells / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D009447:Neuroblastoma; D010300:Parkinson Disease / Q000235:genetics*; D012016:Reference Values; D014407:Tumor Cells, Cultured
chemical_list: D004272:DNA, Mitochondrial; D002374:Catalase; D005979:Glutathione Peroxidase; D009247:NADH, NADPH Oxidoreductases; D005980:Glutathione Reductase; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I