Complex I deficiency is associated with 3243G:C mitochondrial DNA in osteosarcoma cell cybrids.

TitleComplex I deficiency is associated with 3243G:C mitochondrial DNA in osteosarcoma cell cybrids.
Publication TypeJournal Article
Year of Publication1996
AuthorsDunbar, DR, Moonie, PA, Zeviani, M, Holt, IJ
JournalHum Mol Genet
Date Published1996 Jan
KeywordsCell Fusion, DNA, Mitochondrial, Electron Transport Complex IV, Humans, Hybrid Cells, Lactates, Lactic Acid, MELAS Syndrome, Mitochondria, NAD(P)H Dehydrogenase (Quinone), Osteosarcoma, Oxygen Consumption, Point Mutation, Protein Biosynthesis, Pyruvates, Pyruvic Acid, Tumor Cells, Cultured

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.

Alternate JournalHum. Mol. Genet.
Citation Key10.1093/hmg/5.1.123
PubMed ID8789449
Grant List / / Wellcome Trust / United Kingdom