Role of adenine nucleotide translocator 1 in mtDNA maintenance

被引:470
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
相关论文
共 38 条
  • [1] ADENINE-NUCLEOTIDE TRANSLOCATOR DEFICIENCY IN MUSCLE - POTENTIAL THERAPEUTIC VALUE OF VITAMIN-E
    BAKKER, HD
    SCHOLTE, HR
    VANDENBOGERT, C
    JENESON, JAL
    RUITENBEEK, W
    WANDERS, RJA
    ABELING, NGGM
    VANGENNIP, AH
    [J]. JOURNAL OF INHERITED METABOLIC DISEASE, 1993, 16 (03) : 548 - 552
  • [2] Adenine nucleotide translocase-1, a component of the permeability transition pore, can dominantly induce apoptosis
    Bauer, MKA
    Schubert, A
    Rocks, O
    Grimm, S
    [J]. JOURNAL OF CELL BIOLOGY, 1999, 147 (07) : 1493 - 1501
  • [3] ANIMAL AND PLANT-MITOCHONDRIA CONTAIN SPECIFIC THIOREDOXINS
    BODENSTEINLANG, J
    BUCH, A
    FOLLMANN, H
    [J]. FEBS LETTERS, 1989, 258 (01) : 22 - 26
  • [4] Multiple mitochondrial DNA deletions associated with autosomal recessive ophthalmoplegia and severe cardiomyopathy
    Bohlega, S
    Tanji, K
    Santorelli, FM
    Hirano, M
    alJishi, A
    DiMauro, S
    [J]. NEUROLOGY, 1996, 46 (05) : 1329 - 1334
  • [5] Mitochondrial ADP/ATP carrier can be reversibly converted into a large channel by Ca2+
    Brustovetsky, N
    Klingenberg, M
    [J]. BIOCHEMISTRY, 1996, 35 (26) : 8483 - 8488
  • [6] Cellular and molecular studies in muscle and cultures from patients with multiple mitochondrial DNA deletions
    Carrozzo, R
    Davidson, MM
    Walker, WF
    Hirano, M
    Miranda, AF
    [J]. JOURNAL OF THE NEUROLOGICAL SCIENCES, 1999, 170 (01) : 24 - 31
  • [7] Tissue-specific transcription pattern of the adenine nucleotide translocase isoforms in humans
    Doerner, A
    Pauschinger, M
    Badorff, A
    Noutsias, M
    Giessen, S
    Schulze, K
    Bilger, J
    Rauch, U
    Schultheiss, HP
    [J]. FEBS LETTERS, 1997, 414 (02) : 258 - 262
  • [8] YEAST ADP ATP CARRIER (AAC) PROTEINS EXHIBIT SIMILAR ENZYMATIC-PROPERTIES BUT THEIR DELETION PRODUCES DIFFERENT PHENOTYPES
    DRGON, T
    SABOVA, L
    GAVURNIKOVA, G
    KOLAROV, J
    [J]. FEBS LETTERS, 1992, 304 (2-3) : 277 - 280
  • [9] Mitochondrial disease in mouse results in increased oxidative stress
    Esposito, LA
    Melov, S
    Panov, A
    Cottrell, BA
    Wallace, DC
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (09) : 4820 - 4825
  • [10] A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart/muscle isoform of the adenine nucleotide translocator
    Graham, BH
    Waymire, KG
    Cottrell, B
    Trounce, IA
    MacGregor, GR
    Wallace, DC
    [J]. NATURE GENETICS, 1997, 16 (03) : 226 - 234