Complex I deficiency is Associated with 3243G:C Mitochondrial DNA in Osteosarcoma Cell Cybrids

Abstract
143B.206 ρ° 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.