Role of adenine nucleotide translocator 1 in mtDNA maintenance

Autosomal dominant progressive external ophthalmoplegia is a rare human dis ease that shows a Mendelian inheritance pattern, but is characterized by La rge-scale mitochondrial DNA (mtDNA) deletions. We have identified two heter ozygous missense mutations in the nuclear gene encoding the heart/skeletal muscle isoform of the adenine nucleotide translocator (ANT1) in five famili es and one sporadic patient. The familiar mutation substitutes a proline fo r a highly conserved alanine at position 114 in the ANT1 protein. The analo gous mutation in yeast caused a respiratory defect. These results indicate that ANT has a role in mtDNA maintenance and that a mitochondrial disease c an be caused by a dominant mechanism.