title: The mitochondrial DNA mutation at 8993 associated with NARP slows the rate of ATP synthesis in isolated lymphoblast mitochondria.
abstract: Mitochondria were prepared from three lymphoblast cell lines from patients with high percentage copy numbers of the human mtDNA 8993 mutation and compared to those prepared from related and non-related control cell lines. Rates of ATP synthesis with pyruvate/malate, succinate/rotenone, ascorbate/N'N'N'N' tetramethyl phenylene diamine were reduced to 67%, 58% and 54% of the control rates, respectively. The backward reaction measured as oligomycin sensitive ATPase was reduced to an average of 42% of that in controls. This mutation which changes a conserved leucine to an arginine in the putative membrane proton channel of mitochondrial ATPase effectively reduces the overall rate of oxidative phosphorylation.
authors: Department of Biochemistry and Paediatrics, University of Toronto, Ontario, Canada.
authors: Y
authors: Y
authors: Tatuch
authors: B H
authors: BH
authors: Robinson
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000595:Amino Acid Sequence; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D007888:Leigh Disease / Q000235:genetics* / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D009154:Mutation; D006180:Proton-Translocating ATPases / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases