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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Sideroblastic / genetics*
  • Cell Line
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex IV / genetics*
  • Humans
  • Kinetics
  • Mitochondria / enzymology*
  • Mutation*
  • Recombination, Genetic


  • DNA, Mitochondrial
  • Electron Transport Complex IV