Subcomplexes of mitochondrial complex V reveal mutations in mitochondrial DNA.
Complex V, site of the final step in oxidative phosphorylation, uses the proton gradient across the inner mitochondrial membrane for the production of ATP. It is a multi-subunit complex composed of a catalytic domain (F(1)) and a membrane domain (F(0)) linked by two stalks. Subcomplexes of complex V containing the F(1) domain have previously been reported in small series of patients. We report the results in tissue samples and/or cultured skin fibroblasts studied by blue native PAGE followed by activity staining in the gel. Catalytically active subcomplexes of complex V were detected in 66 tissues originating from 53 patients. In 29 of the latter (55%), a mitochondrial DNA (mtDNA) defect was identified. Twelve patients had a pathogenic point mutation in a mitochondrial tRNA, one a large mtDNA deletion, 12 showed mtDNA depletion and four had a mutation in the MT-ATP6 gene. We conclude that the presence of subcomplexes of complex V is a valuable indicator in the detection of mtDNA defects.
Department of Paediatrics, Division of Paediatric Neurology and Metabolism, University Hospital Ghent, Ghent, Belgium.
Joél
J
Smet
Sara
S
Seneca
Boel
B
De Paepe
Ann
A
Meulemans
Helene
H
Verhelst
Jules
J
Leroy
Linda
L
De Meirleir
Willy
W
Lissens
Rudy
R
Van Coster
D000328:Adult; D002648:Child; D004591:Electrophoresis, Polyacrylamide Gel; D017353:Gene Deletion; D006801:Humans; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics*; D017354:Point Mutation; D021122:Protein Subunits / Q000235:genetics*
D021122:Protein Subunits; C021983:complex V (mitochondrial oxidative phosphorylation system); C412204:ATP synthase subunit 6; D025261:Mitochondrial Proton-Translocating ATPases