Bröker S, Meunier B, Rich P, Gattermann N, Hofhaus G
Institut für Biochemie und Biologisch-Medizinisches Forschungszentrum der Heinrich-Heine-Universität, Düsseldorf, Germany.
Eur J Biochem. 1998 Nov 15;258(1):132-8. doi: 10.1046/j.1432-1327.1998.2580132.x.
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.
我们最近描述了患有铁粒幼细胞贫血患者线粒体DNA的异质性突变。这些突变改变了细胞色素氧化酶亚基I中保守的1280位残基和M273，细胞色素氧化酶是线粒体呼吸链的末端酶。作为阐明致病机制的第一步，我们通过将这些患者血小板中的线粒体DNA转移到缺乏线粒体基因组的永久性人类细胞系中，研究了这些突变的生化后果。在转线粒体细胞系中对突变引起的酶变化和细胞能量代谢进行了表征。其中一个突变导致该酶的细胞浓度降低以及相应的活性下降。第二个突变改变了双核中心周围的结构，并迫使细胞更强烈地依赖糖酵解。
