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.
Kaukonen, J., Juselius, J., Tiranti, V., Kyttälä, A., Zeviani, M., Comi, G., Keränen, S., Peltonen, L., & Suomalainen, A. (2000). Role of adenine nucleotide translocator 1 in mtDNA maintenance. Science, 289(5480), 782-785. https://doi.org/10.1126/science.289.5480.782