Hereditary optic neuropathies share a common mitochondrial coupling defect.
Hereditary optic neuropathies are heterogeneous diseases characterized by the degeneration of retinal ganglion cells leading to optic nerve atrophy and impairment of central vision. We found a common coupling defect of oxidative phosphorylation in fibroblasts of patients affected by autosomal dominant optic atrophy (mutations of OPA1), autosomal dominant optic atrophy associated with cataract (mutations of OPA3), and Leber's hereditary optic neuropathy, a disorder associated with point mutations of mitochondrial DNA complex I genes. Interestingly, the energetic defect was significantly more pronounced in Leber's hereditary optic neuropathy and autosomal dominant optic atrophy patients with a more complex phenotype, the so-called plus phenotype.
Chevrollier
Arnaud
A
Institut National de la Santé et de la Recherche Médicale, U694, Départment de Biochimie et Génétique, Centre Hospitalier Universitaire, Angers, France. archevrollier@chu-angers.fr
Guillet
Virginie
V
Loiseau
Dominique
D
Gueguen
Naïg
N
de Crescenzo
Marie-Anne Pou
MA
Verny
Christophe
C
Ferre
Marc
M
Dollfus
Hélène
H
Odent
Sylvie
S
Milea
Dan
D
Goizet
Cyril
C
Amati-Bonneau
Patrizia
P
Procaccio
Vincent
V
Bonneau
Dominique
D
Reynier
Pascal
P
D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D004734:Energy Metabolism / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D015418:Optic Atrophies, Hereditary / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D010085:Oxidative Phosphorylation; D011506:Proteins / Q000235:genetics
C443108:OPA3 protein, human; D011506:Proteins; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human