title: MtDNA mutations associated with sideroblastic anaemia cause a defect of mitochondrial cytochrome c oxidase.
abstract: We have recently described heteroplasmic mutations of mitochondrial DNA in patients suffering from sideroblastic anaemia. The mutations change conserved residues 1280 and M273 in subunit I of cytochrome oxidase, the terminal enzyme of the mitochondrial respiratory chain. As a step towards elucidating the pathogenic mechanism, we studied the biochemical consequences of the mutations by transferring mtDNA from these patients' platelets into a permanent human cell line lacking a mitochondrial genome. Mutation-induced changes of the enzyme and the energy metabolism of the cells were characterised in the transmitochondrial cell lines. One of the mutations resulted in a decreased cellular concentration of the enzyme and a corresponding decrease in activity. The second mutation changed the structure around the binuclear centre and forced the cells to rely more strongly on glycolysis.
authors.affiliation: Institut für Biochemie und Biologisch-Medizinisches Forschungszentrum der Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Bröker
authors.forename: B
authors.initials: B
authors.lastname: Meunier
authors.forename: P
authors.initials: P
authors.lastname: Rich
authors.forename: N
authors.initials: N
authors.lastname: Gattermann
authors.forename: G
authors.initials: G
authors.lastname: Hofhaus
mesh_terms: D000756:Anemia, Sideroblastic / Q000235:genetics*; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology*; D009154:Mutation; D011995:Recombination, Genetic
chemical_list: D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV