Biochemical and molecular analysis of cytochrome c oxidase deficiency in Leigh's syndrome.
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.
Lombes
A
A
Department of Neurology, Columbia University Collge of Physicians and Surgeons, New York, NY.
Nakase
H
H
Tritschler
H J
HJ
Kadenbach
B
B
Bonilla
E
E
DeVivo
D C
DC
Schon
E A
EA
DiMauro
S
S
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