Role of adenine nucleotide translocator 1 in mtDNA maintenance

被引:472
作者
Kaukonen, J
Juselius, JK
Tiranti, V
Kyttälä, A
Zeviani, M
Comi, GP
Keränen, S
Peltonen, L
Suomalainen, A
机构
[1] Natl Publ Hlth Inst, Dept Human Mol Genet, SF-00300 Helsinki, Finland
[2] VTT Biotechnol, Espoo, Finland
[3] Natl Neurol Inst C Besta, Dept Neurol Res, Div Biochem & Genet, Milan, Italy
[4] Univ Milan, Osped Maggiore Policlin, Ist Ricovero & Cura Carattere Sci, Ist Clin Neurol,Ctr Dino Ferrari, Milan, Italy
[5] Univ Calif Los Angeles, Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA
关键词
D O I
10.1126/science.289.5480.782
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 familiar 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.
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页码:782 / 785
页数:4
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