The mitochondrial DNA mutation at 8993 associated with NARP slows the rate of ATP synthesis in isolated lymphoblast mitochondria

Biochem Biophys Res Commun. 1993 Apr 15;192(1):124-8. doi: 10.1006/bbrc.1993.1390.


Mitochondria were prepared from three lymphoblast cell lines from patients with high percentage copy numbers of the human mtDNA 8993 mutation and compared to those prepared from related and non-related control cell lines. Rates of ATP synthesis with pyruvate/malate, succinate/rotenone, ascorbate/N'N'N'N' tetramethyl phenylene diamine were reduced to 67%, 58% and 54% of the control rates, respectively. The backward reaction measured as oligomycin sensitive ATPase was reduced to an average of 42% of that in controls. This mutation which changes a conserved leucine to an arginine in the putative membrane proton channel of mitochondrial ATPase effectively reduces the overall rate of oxidative phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis*
  • Amino Acid Sequence
  • Cell Line
  • DNA, Mitochondrial / genetics*
  • Humans
  • Leigh Disease / genetics*
  • Leigh Disease / metabolism
  • Lymphocytes / metabolism*
  • Mitochondria / metabolism*
  • Molecular Sequence Data
  • Muscles / metabolism
  • Mutation*
  • Proton-Translocating ATPases / metabolism


  • DNA, Mitochondrial
  • Adenosine Triphosphate
  • Proton-Translocating ATPases