title: Ubiquinol-10 ameliorates mitochondrial encephalopathy associated with CoQ deficiency.
abstract: Coenzyme Q10 (CoQ10) deficiency (MIM 607426) causes a mitochondrial syndrome with variability in the clinical presentations. Patients with CoQ10 deficiency show inconsistent responses to oral ubiquinone-10 supplementation, with the highest percentage of unsuccessful results in patients with neurological symptoms (encephalopathy, cerebellar ataxia or multisystemic disease). Failure in the ubiquinone-10 treatment may be the result of its poor absorption and bioavailability, which may be improved by using different pharmacological formulations. In a mouse model (Coq9(X/X)) of mitochondrial encephalopathy due to CoQ deficiency, we have evaluated oral supplementation with water-soluble formulations of reduced (ubiquinol-10) and oxidized (ubiquinone-10) forms of CoQ10. Our results show that CoQ10 was increased in all tissues after supplementation with ubiquinone-10 or ubiquinol-10, with the tissue levels of CoQ10 with ubiquinol-10 being higher than with ubiquinone-10. Moreover, only ubiquinol-10 was able to increase the levels of CoQ10 in mitochondria from cerebrum of Coq9(X/X) mice. Consequently, ubiquinol-10 was more efficient than ubiquinone-10 in increasing the animal body weight and CoQ-dependent respiratory chain complex activities, and reducing the vacuolization, astrogliosis and oxidative damage in diencephalon, septum-striatum and, to a lesser extent, in brainstem. These results suggest that water-soluble formulations of ubiquinol-10 may improve the efficacy of CoQ10 therapy in primary and secondary CoQ10 deficiencies, other mitochondrial diseases and neurodegenerative diseases.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain; Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Armilla, Granada, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: García-Corzo
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain; Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Armilla, Granada, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Luna-Sánchez
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain; Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Armilla, Granada, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Doerrier
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain; Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Armilla, Granada, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ortiz
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain; Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Armilla, Granada, Spain.
authors.forename: Germaine
authors.initials: G
authors.lastname: Escames
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain; Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Armilla, Granada, Spain.
authors.forename: Darío
authors.initials: D
authors.lastname: Acuña-Castroviejo
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain; Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Armilla, Granada, Spain. Electronic address: luisca@ugr.es.
authors.forename: Luis C
authors.initials: LC
authors.lastname: López
mesh_terms: D000818:Animals; D001259:Ataxia / Q000188:drug therapy*; D001927:Brain Diseases / Q000188:drug therapy; D001933:Brain Stem / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects; D004579:Electron Transport / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects*; D028361:Mitochondrial Diseases / Q000188:drug therapy*; D017237:Mitochondrial Encephalomyopathies / Q000188:drug therapy*; D018908:Muscle Weakness / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000172:deficiency* / Q000494:pharmacology
chemical_list: D014451:Ubiquinone; C026663:ubiquinol-10; C025204:Ubiquinone Q2
keywords: CoQ(10) deficiency; Mitochondrial encephalopathy; Mouse model; Ubiquinol-10