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Science 4 August 2000:
Vol. 289. no. 5480, pp. 782 - 785
DOI: 10.1126/science.289.5480.782
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Role of Adenine Nucleotide Translocator 1 in mtDNA Maintenance

Jyrki Kaukonen,1 Jukka K. Juselius,2* Valeria Tiranti,3* Aija Kyttälä,1 Massimo Zeviani,3 Giacomo P. Comi,4 Sirkka Keränen,2 Leena Peltonen,15 Anu Suomalainen1dagger

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.

1 National Public Health Institute, Department of Human Molecular Genetics, Mannerheimintie 166, 00300 Helsinki, Finland.
2 VTT Biotechnology, Espoo, Finland.
3 Division of Biochemistry and Genetics, Department of Neurological Research, National Neurological Institute "C. Besta," Milan, Italy.
4 Centro Dino Ferrari, Istituto di Clinica Neurologica, Università degli Studi di Milano, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Maggiore Policlinico, Milan, Italy.
5 Department of Human Genetics, University of California School of Medicine, Los Angeles, CA 10095-7088, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: anu{at}ericpc.mni.mcgill.ca

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