title: Mitochondria in sporadic amyotrophic lateral sclerosis.
abstract: Mitochondria are abnormal in persons with amyotrophic lateral sclerosis (ALS) for unknown reasons. We explored whether aberration of mitochondrial DNA (mtDNA) could play a role in this by transferring mitochondrial DNA (mtDNA) from ALS subjects to mtDNA-depleted human neuroblastoma cells. Resulting ALS cytoplasmic hybrids (cybrids) exhibited abnormal electron transport chain functioning, increases in free radical scavenging enzyme activities, perturbed calcium homeostasis, and altered mitochondrial ultrastructure. Recapitulation of defects previously observed in ALS subjects and ALS transgenic mice by expression of ALS mtDNA support a pathophysiologic role for mtDNA mutation in some persons with this disease.
authors.affiliation: Department of Neurology, University of Virginia Health Sciences Center, 1 Hospital Drive, Charlottesville, Virginia 22908, 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: P A
authors.initials: PA
authors.lastname: Trimmer
authors.forename: S W
authors.initials: SW
authors.lastname: Miller
authors.forename: D J
authors.initials: DJ
authors.lastname: Maguire
authors.forename: J P
authors.initials: JP
authors.lastname: Sheehan
authors.forename: R S
authors.initials: RS
authors.lastname: Maguire
authors.forename: G
authors.initials: G
authors.lastname: Pattee
authors.forename: V C
authors.initials: VC
authors.lastname: Juel
authors.forename: L H
authors.initials: LH
authors.lastname: Phillips
authors.forename: J B
authors.initials: JB
authors.lastname: Tuttle
authors.forename: J P
authors.initials: JP
authors.lastname: Bennett
authors.forename: R E
authors.initials: RE
authors.lastname: Davis
authors.forename: W D
authors.initials: WD
authors.lastname: Parker
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D004579:Electron Transport / Q000235:genetics / Q000502:physiology; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D006822:Hybrid Cells; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D016166:Free Radical Scavengers; D015655:1-Methyl-4-phenylpyridinium; D002118:Calcium