title: CoQ deficiency causes disruption of mitochondrial sulfide oxidation, a new pathomechanism associated with this syndrome.
abstract: Coenzyme Q (CoQ) is a key component of the mitochondrial respiratory chain, but it also has several other functions in the cellular metabolism. One of them is to function as an electron carrier in the reaction catalyzed by sulfide:quinone oxidoreductase (SQR), which catalyzes the first reaction in the hydrogen sulfide oxidation pathway. Therefore, SQR may be affected by CoQ deficiency. Using human skin fibroblasts and two mouse models with primary CoQ deficiency, we demonstrate that severe CoQ deficiency causes a reduction in SQR levels and activity, which leads to an alteration of mitochondrial sulfide metabolism. In cerebrum of Coq9R239Xmice, the deficit in SQR induces an increase in thiosulfate sulfurtransferase and sulfite oxidase, as well as modifications in the levels of thiols. As a result, biosynthetic pathways of glutamate, serotonin, and catecholamines were altered in the cerebrum, and the blood pressure was reduced. Therefore, this study reveals the reduction in SQR activity as one of the pathomechanisms associated with CoQ deficiency syndrome.
authors.affiliation: Departmento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain martalunasan@ugr.es luisca@ugr.es.|Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Luna-Sánchez
authors.affiliation: Departmento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain.|Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain.
authors.forename: Agustín
authors.initials: A
authors.lastname: Hidalgo-Gutiérrez
authors.affiliation: Institut für Pflanzengenetik, Leibniz Universität Hannover, Hannover, Germany.
authors.forename: Tatjana M
authors.initials: TM
authors.lastname: Hildebrandt
authors.affiliation: Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Chaves-Serrano
authors.affiliation: Departmento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain.|Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain.
authors.forename: Eliana
authors.initials: E
authors.lastname: Barriocanal-Casado
authors.affiliation: Abbott Nutrition, R&D, Abbott Laboratories, Granada, Spain.
authors.forename: Ángela
authors.initials: Á
authors.lastname: Santos-Fandila
authors.affiliation: Departmento de Farmacología, Facultad de Farmacia, Instituto de Investigación Biosanitaria de Granada, Universidad de Granada, Granada, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Romero
authors.affiliation: Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain.|Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Sohag University, Sohag, Egypt.
authors.forename: Ramy Ka
authors.initials: RK
authors.lastname: Sayed
authors.affiliation: Departmento de Farmacología, Facultad de Farmacia, Instituto de Investigación Biosanitaria de Granada, Universidad de Granada, Granada, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Duarte
authors.affiliation: Institute of Human Genetics, Technische Universität München, München, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Prokisch
authors.affiliation: Department of Neuropediatrics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Markus
authors.identifier: 0000-0003-2824-3891
authors.initials: M
authors.lastname: Schuelke
authors.affiliation: Department of General Pediatrics, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Distelmaier
authors.affiliation: Departmento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain.|Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain.
authors.forename: Germaine
authors.initials: G
authors.lastname: Escames
authors.affiliation: Departmento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain.|Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain.
authors.forename: Darío
authors.initials: D
authors.lastname: Acuña-Castroviejo
authors.affiliation: Departmento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain martalunasan@ugr.es luisca@ugr.es.|Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain.
authors.forename: Luis C
authors.identifier: 0000-0003-3355-0298
authors.initials: LC
authors.lastname: López
mesh_terms: D000818:Animals; D001259:Ataxia / Q000503:physiopathology*; D001794:Blood Pressure; D002478:Cells, Cultured; D054022:Cerebrum / Q000503:physiopathology; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000503:physiopathology*; D018908:Muscle Weakness / Q000503:physiopathology*; D010084:Oxidation-Reduction; D011808:Quinone Reductases / Q000378:metabolism*; D013440:Sulfides / Q000378:metabolism*; D014451:Ubiquinone / Q000172:deficiency*
chemical_list: D013440:Sulfides; D014451:Ubiquinone; D011808:Quinone Reductases; C073412:sulfide quinone reductase
keywords: 
  COX
  ; 
  SQR
  ; blood pressure; glutathione; mitochondrial disease