MtDNA mutations associated with sideroblastic anaemia cause a defect of mitochondrial cytochrome c oxidase.
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Broker S, Meunier B, Rich P, Gattermann N, Hofhaus G
MtDNA mutations associated with sideroblastic anaemia cause a defect of mitochondrial cytochrome c oxidase.
Eur J Biochem. 1998 Nov 15;258(1):132-8.
- PubMed ID
- 9851701 [ View in PubMed]
- 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.