A novel D104G mutation in the adenine nucleotide translocator 1 gene in autosomal dominant progressive external ophthalmoplegia patients with mitochondrial DNA with multiple deletions

2002 ◽  
Vol 51 (5) ◽  
pp. 645-648 ◽  
Author(s):  
Hirofumi Komaki ◽  
Toshiyuki Fukazawa ◽  
Hideki Houzen ◽  
Kazuto Yoshida ◽  
Ikuya Nonaka ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Autosomal Dominant ◽  
Adenine Nucleotide ◽  
Progressive External Ophthalmoplegia ◽  
Adenine Nucleotide Translocator ◽  
Adenine Nucleotide Translocator 1

scholarly journals Suppression of Mitochondrial DNA Instability of Autosomal Dominant Forms of Progressive External Ophthalmoplegia-Associated ANT1 Mutations in Podospora anserina

Genetics ◽  
2009 ◽  
Vol 183 (3) ◽  
pp. 861-871 ◽  
Author(s):  
Riyad El-Khoury ◽  
Annie Sainsard-Chanet
Keyword(s):  
Mitochondrial Dna ◽  
Membrane Potential ◽  
Large Scale ◽  
Autosomal Dominant ◽  
Adenine Nucleotide ◽  
Podospora Anserina ◽  
Progressive External Ophthalmoplegia ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Mtdna Deletions

Maintenance and expression of mitochondrial DNA (mtDNA) are essential for the cell and the organism. In humans, several mutations in the adenine nucleotide translocase gene ANT1 are associated with multiple mtDNA deletions and autosomal dominant forms of progressive external ophthalmoplegia (adPEO). The mechanisms underlying the mtDNA instability are still obscure. A current hypothesis proposes that these pathogenic mutations primarily uncouple the mitochondrial inner membrane, which secondarily causes mtDNA instability. Here we show that the three adPEO-associated mutations equivalent to A114P, L98P, and V289M introduced into the Podospora anserina ANT1 ortholog dominantly cause severe growth defects, decreased reactive oxygen species production (ROS), decreased mitochondrial inner membrane potential (Δψ), and accumulation of large-scale mtDNA deletions leading to premature death. Interestingly, we show that, at least for the adPEO-type M106P and A121P mutant alleles, the associated mtDNA instability cannot be attributed only to a reduced membrane potential or to an increased ROS level since it can be suppressed without restoration of the Δψ or modification of the ROS production. Suppression of mtDNA instability due to the M106P and A121P mutations was obtained by an allele of the rmp1 gene involved in nucleo-mitochondrial cross- talk and also by an allele of the AS1 gene encoding a cytosolic ribosomal protein. In contrast, the mtDNA instability caused by the S296M mutation was not suppressed by these alleles.

Lack of apoptosis in patients with progressive external ophthalmoplegia and mutated adenine nucleotide translocator-1 gene

2002 ◽  
Vol 26 (2) ◽  
pp. 265-269 ◽  
Author(s):  
Gigliola Fagiolari ◽  
Monica Sciacco ◽  
Luca Chiveri ◽  
Costanza Lamperti ◽  
Giacomo Pietro Comi ◽  
...  
Keyword(s):  
Adenine Nucleotide ◽  
Progressive External Ophthalmoplegia ◽  
Adenine Nucleotide Translocator ◽  
Adenine Nucleotide Translocator 1

Mutations of mitochondrial DNA polymerase ?A are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia

2002 ◽  
Vol 52 (2) ◽  
pp. 211-219 ◽  
Author(s):  
Eleonora Lamantea ◽  
Valeria Tiranti ◽  
Andreina Bordoni ◽  
Antonio Toscano ◽  
Francesco Bono ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Dna Polymerase ◽  
Autosomal Dominant ◽  
Progressive External Ophthalmoplegia ◽  
Mitochondrial Dna Polymerase
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