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Subcomplexes of mitochondrial complex V reveal mutations in mitochondrial DNA
Author(s) -
Smet Joél,
Seneca Sara,
De Paepe Boel,
Meulemans Ann,
Verhelst Helene,
Leroy Jules,
De Meirleir Linda,
Lissens Willy,
Van Coster Rudy
Publication year - 2009
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.200900213
Subject(s) - mitochondrial dna , inner mitochondrial membrane , biology , microbiology and biotechnology , protein subunit , point mutation , mitochondrion , mutation , oxidative phosphorylation , genetics , gene , biochemistry
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.