Role of adenine nucleotide translocator 1 in mtDNA maintenance.

TitleRole of adenine nucleotide translocator 1 in mtDNA maintenance.
Publication TypeJournal Article
Year of Publication2000
AuthorsKaukonen, J, Juselius, JK, Tiranti, V, Kyttälä, A, Zeviani, M, Comi, GP, Keränen, S, Peltonen, L, Suomalainen, A
Date Published2000 Aug 04
KeywordsAmino Acid Sequence, Amino Acid Substitution, Animals, DNA, Mitochondrial, Female, Founder Effect, Genes, Dominant, Humans, Isoenzymes, Italy, Male, Mitochondrial ADP, ATP Translocases, Molecular Sequence Data, Mutation, Missense, Ophthalmoplegia, Chronic Progressive External, Oxygen Consumption, Pedigree, Point Mutation, Saccharomyces cerevisiae, Sequence Deletion, Transformation, Genetic

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.

Alternate JournalScience
Citation Key10.1126/science.289.5480.782
PubMed ID10926541
Grant List1180 / / Telethon / Italy