MtDNA mutations associated with sideroblastic anaemia cause a defect of mitochondrial cytochrome c oxidase

被引:29
作者
Bröker, S
Meunier, B
Rich, P
Gattermann, N
Hofhaus, G
机构
[1] Univ Dusseldorf, Inst Biochem & Biol, Med Forschungszentrum, D-4000 Dusseldorf, Germany
[2] UCL, Dept Biol, London WC1E 6BT, England
[3] Univ Dusseldorf, Abt Haematol Onkol & Klin Immunol, D-4000 Dusseldorf, Germany
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 1998年 / 258卷 / 01期
关键词
cytochrome oxidase; laser-flash photolysis; transmitochondrial cell lines; sideroblastic anaemia;
D O I
10.1046/j.1432-1327.1998.2580132.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have recently described heteroplasmic mutations of mitochondrial DNA in patients suffering from sideroblastic anaemia. The mutations change conserved residues I280 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.
引用
收藏
页码:132 / 138
页数:7
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