Complex I deficiency is associated with 3243G:C mitochondrial DNA in osteosarcoma cell cybrids.
143B.206 rho degrees cells were repopulated with mitochondria from a MELAS patient harbouring a mixture of 3243G:C and 3243A:T mitochondrial DNA. A number of biochemical assays were performed on selected cybrids with various proportions of the two types of mitochondrial DNA. These assays revealed a marked decrease in oxygen consumption with pyruvate, a complex I substrate, in cybrids containing 60% to 90% 3243G:C mitochondrial DNA. Moreover, these cybrids showed decreased synthesis of a number of polypeptides in a mitochondrial in vitro translation assay. A cybrid line with a very high level of 3243G:C mitochondrial DNA (95%) had additional deficiencies in complexes III and IV and there was a marked generalised decrease in mitochondrial translation in this cybrid. The observation of complex I deficiency is consistent with previously reported enzymatic measurements of muscle homogenates from MELAS patients with the 3243G:C mutation.
Dunbar
D R
DR
Department of Biochemical Medicine, Ninewells Hospital, Dundee, UK.
Moonie
P A
PA
Zeviani
M
M
Holt
I J
IJ
D002459:Cell Fusion; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D006822:Hybrid Cells; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D017241:MELAS Syndrome / Q000201:enzymology / Q000235:genetics*; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D012516:Osteosarcoma; D010101:Oxygen Consumption; D017354:Point Mutation; D014176:Protein Biosynthesis; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D014407:Tumor Cells, Cultured
D004272:DNA, Mitochondrial; D007773:Lactates; D011773:Pyruvates; D019344:Lactic Acid; D019289:Pyruvic Acid; D016660:NAD(P)H Dehydrogenase (Quinone); D003576:Electron Transport Complex IV