Role of adenine nucleotide translocator 1 in mtDNA maintenance

Science. 2000 Aug 4;289(5480):782-5. doi: 10.1126/science.289.5480.782.

Abstract

Autosomal dominant progressive external ophthalmoplegia is a rare human disease that shows a Mendelian inheritance pattern, but is characterized by large-scale mitochondrial DNA (mtDNA) deletions. We have identified two heterozygous missense mutations in the nuclear gene encoding the heart/skeletal muscle isoform of the adenine nucleotide translocator (ANT1) in five families and one sporadic patient. The familial mutation substitutes a proline for a highly conserved alanine at position 114 in the ANT1 protein. The analogous mutation in yeast caused a respiratory defect. These results indicate that ANT has a role in mtDNA maintenance and that a mitochondrial disease can be caused by a dominant mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / metabolism*
  • Female
  • Founder Effect
  • Genes, Dominant
  • Humans
  • Isoenzymes / chemistry
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Italy
  • Male
  • Mitochondrial ADP, ATP Translocases / chemistry
  • Mitochondrial ADP, ATP Translocases / genetics*
  • Mitochondrial ADP, ATP Translocases / metabolism*
  • Molecular Sequence Data
  • Mutation, Missense
  • Ophthalmoplegia, Chronic Progressive External / enzymology
  • Ophthalmoplegia, Chronic Progressive External / genetics*
  • Oxygen Consumption
  • Pedigree
  • Point Mutation
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Sequence Deletion
  • Transformation, Genetic

Substances

  • DNA, Mitochondrial
  • Isoenzymes
  • Mitochondrial ADP, ATP Translocases

Grant support