title: Evaluating the therapeutic potential of idebenone and related quinone analogues in Leber hereditary optic neuropathy.
abstract: Leber hereditary optic neuropathy (LHON) is an important cause of mitochondrial blindness among young adults. In this study, we investigated the potential of four quinone analogues (CoQ1, CoQ10, decylubiquinone and idebenone) in compensating for the deleterious effect of the m.11778G>A mitochondrial DNA mutation. The LHON fibroblast cell lines tested exhibited reduced cell growth, impaired mitochondrial bioenergetics and elevated levels of reactive oxygen species (ROS). Idebenone increased ATP production and reduced ROS levels, but the effect was partial and cell-specific. The remaining quinone analogues had variable effects and a negative impact on certain mitochondrial parameters was observed in some cell lines.
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne, UK; NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK; Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge, UK. Electronic address: Patrick.Yu-Wai-Man@ncl.ac.uk.
authors.forename: Patrick
authors.initials: P
authors.lastname: Yu-Wai-Man
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Department of Genetics and Metabolic Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Devorah
authors.initials: D
authors.lastname: Soiferman
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: David G
authors.initials: DG
authors.lastname: Moore
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Florence
authors.initials: F
authors.lastname: Burté
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Department of Genetics and Metabolic Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Ann
authors.initials: A
authors.lastname: Saada
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000293:Adolescent; D000975:Antioxidants / Q000378:metabolism*; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D029242:Optic Atrophy, Hereditary, Leber / Q000473:pathology*; D011809:Quinones / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000032:analysis*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000975:Antioxidants; D011809:Quinones; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D000255:Adenosine Triphosphate; C036619:idebenone
keywords: Coenzyme Q(10); Idebenone; Leber hereditary optic neuropathy; Mitochondrial disease; Optic atrophy; Quinone