title: Mitochondrial DNA and respiratory chain function in spinal cords of ALS patients.
abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective motor neuron death. In order to address the question of a putative role of mitochondrial dysfunction in the pathogenesis of ALS, we studied the mitochondrial DNA (mtDNA) and mitochondrial respiratory chain enzyme activities in spinal cords of ALS patients and in control subjects without neuropathologic abnormalities. Using a "double PCR and digestion" technique to estimate the levels of randomly distributed point mutations in two small regions of the mtDNA, we found significantly higher levels of mutant mtDNA in the spinal cord of ALS patients compared to controls. No large-scale rearrangements were found, but the amount of mtDNA, measured by Southern blot, was significantly lower in the ALS samples. This reduction correlated well with a decrease of citrate synthase (CS) activity, a mitochondrial marker, as were the activities of respiratory chain complexes I + III, II + III, and IV, suggesting a loss of mitochondria in ALS spinal cords.
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, USA. falk.wiedemann@medizin.uni-magdeburg.de
authors.forename: Falk R
authors.initials: FR
authors.lastname: Wiedemann
authors.forename: Giovanni
authors.initials: G
authors.lastname: Manfredi
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.forename: M Flint
authors.initials: MF
authors.lastname: Beal
authors.forename: Eric A
authors.initials: EA
authors.lastname: Schon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D015139:Blotting, Southern; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000032:analysis / Q000378:metabolism*; D004579:Electron Transport; D042967:Electron Transport Complex I; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D013116:Spinal Cord / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004272:DNA, Mitochondrial; D009097:Multienzyme Complexes; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D009247:NADH, NADPH Oxidoreductases; D003576:Electron Transport Complex IV; D002795:Choline O-Acetyltransferase; D002950:Citrate (si)-Synthase; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III