title: Biochemical and molecular analysis of cytochrome c oxidase deficiency in Leigh's syndrome.
abstract: We studied three patients with Leigh's syndrome (LS) and cytochrome c oxidase (COX) deficiency. Biochemical studies in brain, muscle, heart, liver, kidney, and fibroblasts disclosed a generalized COX deficiency. Kinetic studies of COX activity in brain mitochondria showed a low Vmax and a normal Km for reduced cytochrome c. Immunologic studies showed decrease of all COX subunits studied, without a specific defect of any one of them. Southern blot analysis excluded large deletions of mitochondrial DNA (mtDNA) but revealed a generalized increase in mtDNA quantity. Although Northern blot analysis showed no alteration in the 12 COX subunit mRNAs studied, two of three patients showed a decreased steady state rate of COX transcription in brain. COX deficiency in LS thus appears to be related to a decreased amount of otherwise normal COX holoenzyme.
authors.affiliation: Department of Neurology, Columbia University Collge of Physicians and Surgeons, New York, NY.
authors.forename: A
authors.initials: A
authors.lastname: Lombes
authors.forename: H
authors.initials: H
authors.lastname: Nakase
authors.forename: H J
authors.initials: HJ
authors.lastname: Tritschler
authors.forename: B
authors.initials: B
authors.lastname: Kadenbach
authors.forename: E
authors.initials: E
authors.lastname: Bonilla
authors.forename: D C
authors.initials: DC
authors.lastname: DeVivo
authors.forename: E A
authors.initials: EA
authors.lastname: Schon
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D001671:Biochemistry / Q000379:methods; D030401:Cytochrome-c Oxidase Deficiency; D004200:Diseases in Twins; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007888:Leigh Disease / Q000201:enzymology*; D008297:Male; D008967:Molecular Biology