Role of adenine nucleotide translocator 1 in mtDNA maintenance.
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.
National Public Health Institute, Department of Human Molecular Genetics, Mannerheimintie 166, 00300 Helsinki, Finland.
J
J
Kaukonen
J K
JK
Juselius
V
V
Tiranti
A
A
Kyttälä
M
M
Zeviani
G P
GP
Comi
S
S
Keränen
L
L
Peltonen
A
A
Suomalainen
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D018703:Founder Effect; D005799:Genes, Dominant; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007558:Italy; D008297:Male; D000226:Mitochondrial ADP, ATP Translocases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017246:Ophthalmoplegia, Chronic Progressive External / Q000201:enzymology / Q000235:genetics*; D010101:Oxygen Consumption; D010375:Pedigree; D017354:Point Mutation; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014170:Transformation, Genetic
D004272:DNA, Mitochondrial; D007527:Isoenzymes; D000226:Mitochondrial ADP, ATP Translocases