A novel mtDNA mutation in the ATPase6 gene studied by E. coli modeling

Neurol Sci. 2000;21(5 Suppl):S983-4. doi: 10.1007/s100720070016.

Abstract

This study aimed to understand the pathogenesis of a new mtDNA-related etiology of Leigh syndrome. We identified the T9176G mutation as the molecular basis of Leigh syndrome in a child and looked for alterations in cellular ATP production. We then modeled the new mtDNA mutation in E. coli and analyzed ATP synthesis, hydrolysis, and the ability of the mutated enzyme to pump protons. Our results suggest that the T9176G change results in a novel, fully assembled enzyme which inhibits the holoenzyme probably by blocking the proton pathway.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / biosynthesis*
  • Adenosine Triphosphate / genetics*
  • Brain / enzymology
  • Brain / pathology
  • Brain / physiopathology
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics*
  • Electron Transport / genetics
  • Escherichia coli / genetics*
  • Female
  • Genes / genetics
  • Humans
  • Leigh Disease / enzymology
  • Leigh Disease / genetics*
  • Leigh Disease / physiopathology
  • Models, Genetic
  • Point Mutation / genetics*
  • Protein Structure, Tertiary / genetics

Substances

  • DNA, Mitochondrial
  • Adenosine Triphosphate
  • Adenosine Triphosphatases