title: Hereditary optic neuropathies share a common mitochondrial coupling defect.
abstract: 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.
authors.affiliation: 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
authors.forename: Arnaud
authors.initials: A
authors.lastname: Chevrollier
authors.forename: Virginie
authors.initials: V
authors.lastname: Guillet
authors.forename: Dominique
authors.initials: D
authors.lastname: Loiseau
authors.forename: Naïg
authors.initials: N
authors.lastname: Gueguen
authors.forename: Marie-Anne Pou
authors.initials: MA
authors.lastname: de Crescenzo
authors.forename: Christophe
authors.initials: C
authors.lastname: Verny
authors.forename: Marc
authors.initials: M
authors.lastname: Ferre
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
authors.forename: Sylvie
authors.initials: S
authors.lastname: Odent
authors.forename: Dan
authors.initials: D
authors.lastname: Milea
authors.forename: Cyril
authors.initials: C
authors.lastname: Goizet
authors.forename: Patrizia
authors.initials: P
authors.lastname: Amati-Bonneau
authors.forename: Vincent
authors.initials: V
authors.lastname: Procaccio
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonneau
authors.forename: Pascal
authors.initials: P
authors.lastname: Reynier
mesh_terms: 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
chemical_list: C443108:OPA3 protein, human; D011506:Proteins; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human