title: Characterization of cybrid cell lines containing mtDNA from Huntington's disease patients.
abstract: Electron transport chain (ETC) dysfunction may arise from mitochondrial genetic, nuclear genetic, or toxic etiologies. Cytoplasmic hybrid (cybrid) systems can help distinguish between these possibilities by facilitating expression of suspect mitochondrial DNA (mtDNA) within a nuclear and environmentally controlled context. Perpetuation of ETC dysfunction in cybrids is consistent with an mtDNA pathogenesis while defect correction is not. We previously used cybrids to screen sporadic Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis patients for mtDNA mutation with positive results. To further address the fidelity of these experiments, we created and characterized cybrids expressing mtDNA from persons with Huntington's disease (HD), an autosomal dominant, nuclear DNA-determined disorder in which mitochondrial ETC functioning is abnormal. On ETC, oxidative stress, and calcium homeostasis assays HD cybrid lines were indistinguishable from control cybrid lines. These data support the use of the cybrid technique for mtDNA mutation screening in candidate diseases.
authors.affiliation: Center for the Study of Neurodegenerative Diseases, University of Virginia Health Sciences Center, Charlottesville, Virginia, 22908, USA.rhs7e@virginia.edu
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: A T
authors.initials: AT
authors.lastname: Shilling
authors.forename: J P
authors.initials: JP
authors.lastname: Bennett
authors.forename: M B
authors.initials: MB
authors.lastname: Harrison
authors.forename: W D
authors.initials: WD
authors.lastname: Parker
mesh_terms: D000328:Adult; D002118:Calcium / Q000378:metabolism; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics*; D004579:Electron Transport; D015870:Gene Expression; D006801:Humans; D006816:Huntington Disease / Q000235:genetics*; D006822:Hybrid Cells / Q000378:metabolism / Q000648:ultrastructure*; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D011808:Quinone Reductases; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D004272:DNA, Mitochondrial; D014475:Uncoupling Agents; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D011808:Quinone Reductases; D002118:Calcium