title: The CoQH2/CoQ Ratio Serves as a Sensor of Respiratory Chain Efficiency.
abstract: Electrons feed into the mitochondrial electron transport chain (mETC) from NAD- or FAD-dependent enzymes. A shift from glucose to fatty acids increases electron flux through FAD, which can saturate the oxidation capacity of the dedicated coenzyme Q (CoQ) pool and result in the generation of reactive oxygen species. To prevent this, the mETC superstructure can be reconfigured through the degradation of respiratory complex I, liberating associated complex III to increase electron flux via FAD at the expense of NAD. Here, we demonstrate that this adaptation is driven by the ratio of reduced to oxidized CoQ. Saturation of CoQ oxidation capacity induces reverse electron transport from reduced CoQ to complex I, and the resulting local generation of superoxide oxidizes specific complex I proteins, triggering their degradation and the disintegration of the complex. Thus, CoQ redox status acts as a metabolic sensor that fine-tunes mETC configuration in order to match the prevailing substrate profile.
authors.affiliation: Departamento de Desarrollo y Reparación Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
authors.forename: Adela
authors.initials: A
authors.lastname: Guarás
authors.affiliation: Departamento de Desarrollo y Reparación Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Perales-Clemente
authors.affiliation: Laboratorio de Proteómica Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Calvo
authors.affiliation: Departamento de Desarrollo y Reparación Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Acín-Pérez
authors.affiliation: Laboratorio de Proteómica Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Loureiro-Lopez
authors.affiliation: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany; Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
authors.forename: Claire
authors.initials: C
authors.lastname: Pujol
authors.affiliation: Departamento de Desarrollo y Reparación Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Martínez-Carrascoso
authors.affiliation: Laboratorio de Proteómica Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Nuñez
authors.affiliation: Laboratorio de Proteómica Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: García-Marqués
authors.affiliation: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, Sevilla 41013, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Sevilla 41013, Spain.
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Rodríguez-Hernández
authors.affiliation: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, Sevilla 41013, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Sevilla 41013, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Cortés
authors.affiliation: Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Francisca
authors.initials: F
authors.lastname: Diaz
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza 50009, Spain.
authors.forename: Acisclo
authors.initials: A
authors.lastname: Pérez-Martos
authors.affiliation: Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; Department of Cell Biology and Anatomy, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Carlos T
authors.initials: CT
authors.lastname: Moraes
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza 50009, Spain.
authors.forename: Patricio
authors.initials: P
authors.lastname: Fernández-Silva
authors.affiliation: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany; Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Trifunovic
authors.affiliation: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, Sevilla 41013, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Sevilla 41013, Spain.
authors.forename: Plácido
authors.initials: P
authors.lastname: Navas
authors.affiliation: Laboratorio de Proteómica Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Vazquez
authors.affiliation: Departamento de Desarrollo y Reparación Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza 50009, Spain. Electronic address: jaenriquez@cnic.es.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Enríquez
mesh_terms: D000818:Animals; D002460:Cell Line; D004579:Electron Transport; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009243:NAD / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism*
chemical_list: D045222:Electron Transport Chain Complex Proteins; D017382:Reactive Oxygen Species; D009243:NAD; D014451:Ubiquinone; D005182:Flavin-Adenine Dinucleotide