Role of adenine nucleotide translocator 1 in mtDNA maintenance

Jyrki Kaukonen, Jukka Juselius, Valeria Tiranti, Aija Kyttälä, Massimo Zeviani, Giacomo Comi, Sirkka Keränen, Leena Peltonen, Anu Suomalainen

Research output: Contribution to journalArticleScientificpeer-review

477 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)782 - 785
Number of pages4
JournalScience
Volume289
Issue number5480
DOIs
Publication statusPublished - 2000
MoE publication typeA1 Journal article-refereed

Fingerprint

Adenine Nucleotide Translocator 1
Mitochondrial DNA
Chronic Progressive External Ophthalmoplegia
Maintenance
Mitochondrial Diseases
Inheritance Patterns
Mutation
Missense Mutation
Rare Diseases
Proline
Alanine
Myocardium
Skeletal Muscle
Yeasts
Genes
Proteins

Cite this

Kaukonen, J., Juselius, J., Tiranti, V., Kyttälä, A., Zeviani, M., Comi, G., ... 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
Kaukonen, Jyrki ; Juselius, Jukka ; Tiranti, Valeria ; Kyttälä, Aija ; Zeviani, Massimo ; Comi, Giacomo ; Keränen, Sirkka ; Peltonen, Leena ; Suomalainen, Anu. / Role of adenine nucleotide translocator 1 in mtDNA maintenance. In: Science. 2000 ; Vol. 289, No. 5480. pp. 782 - 785.
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abstract = "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.",
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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, vol. 289, no. 5480, pp. 782 - 785. https://doi.org/10.1126/science.289.5480.782

Role of adenine nucleotide translocator 1 in mtDNA maintenance. / Kaukonen, Jyrki; Juselius, Jukka; Tiranti, Valeria; Kyttälä, Aija; Zeviani, Massimo; Comi, Giacomo; Keränen, Sirkka; Peltonen, Leena; Suomalainen, Anu.

In: Science, Vol. 289, No. 5480, 2000, p. 782 - 785.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Role of adenine nucleotide translocator 1 in mtDNA maintenance

AU - Kaukonen, Jyrki

AU - Juselius, Jukka

AU - Tiranti, Valeria

AU - Kyttälä, Aija

AU - Zeviani, Massimo

AU - Comi, Giacomo

AU - Keränen, Sirkka

AU - Peltonen, Leena

AU - Suomalainen, Anu

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

U2 - 10.1126/science.289.5480.782

DO - 10.1126/science.289.5480.782

M3 - Article

VL - 289

SP - 782

EP - 785

JO - Science

JF - Science

SN - 0036-8075

IS - 5480

ER -

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