title: Oxygen Sensing by Arterial Chemoreceptors Depends on Mitochondrial Complex I Signaling.
abstract: O2 sensing is essential for mammalian homeostasis. Peripheral chemoreceptors such as the carotid body (CB) contain cells with O2-sensitive K(+) channels, which are inhibited by hypoxia to trigger fast adaptive cardiorespiratory reflexes. How variations of O2 tension (PO2) are detected and the mechanisms whereby these changes are conveyed to membrane ion channels have remained elusive. We have studied acute O2 sensing in conditional knockout mice lacking mitochondrial complex I (MCI) genes. We inactivated Ndufs2, which encodes a protein that participates in ubiquinone binding. Ndufs2-null mice lose the hyperventilatory response to hypoxia, although they respond to hypercapnia. Ndufs2-deficient CB cells have normal functions and ATP content but are insensitive to changes in PO2. Our data suggest that chemoreceptor cells have a specialized succinate-dependent metabolism that induces an MCI state during hypoxia, characterized by the production of reactive oxygen species and accumulation of reduced pyridine nucleotides, which signal neighboring K(+) channels.
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Campus Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013 Seville, Spain; Departamento de Fisiología Médica y Biofísica, Facultad de Medicina, Universidad de Sevilla, Avenida Sánchez Pizjuan, 4, 41009 Seville, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Campus Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013 Seville, Spain.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Fernández-Agüera
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Campus Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013 Seville, Spain; Departamento de Fisiología Médica y Biofísica, Facultad de Medicina, Universidad de Sevilla, Avenida Sánchez Pizjuan, 4, 41009 Seville, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Campus Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013 Seville, Spain.
authors.forename: Lin
authors.initials: L
authors.lastname: Gao
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Campus Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013 Seville, Spain; Departamento de Fisiología Médica y Biofísica, Facultad de Medicina, Universidad de Sevilla, Avenida Sánchez Pizjuan, 4, 41009 Seville, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Campus Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013 Seville, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: González-Rodríguez
authors.affiliation: Centro de Producción y Experimentación Animal, Universidad de Sevilla, Calle San Fernando, 4, 41004 Seville, Spain.
authors.forename: C Oscar
authors.initials: CO
authors.lastname: Pintado
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Campus Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013 Seville, Spain; Departamento de Fisiología Médica y Biofísica, Facultad de Medicina, Universidad de Sevilla, Avenida Sánchez Pizjuan, 4, 41009 Seville, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Campus Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013 Seville, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Arias-Mayenco
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Campus Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013 Seville, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Campus Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013 Seville, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: García-Flores
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Campus Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013 Seville, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: García-Pergañeda
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Campus Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013 Seville, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pascual
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Campus Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013 Seville, Spain; Departamento de Fisiología Médica y Biofísica, Facultad de Medicina, Universidad de Sevilla, Avenida Sánchez Pizjuan, 4, 41009 Seville, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Campus Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013 Seville, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ortega-Sáenz
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Campus Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013 Seville, Spain; Departamento de Fisiología Médica y Biofísica, Facultad de Medicina, Universidad de Sevilla, Avenida Sánchez Pizjuan, 4, 41009 Seville, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Campus Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013 Seville, Spain. Electronic address: lbarneo@us.es.
authors.forename: José
authors.initials: J
authors.lastname: López-Barneo
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002344:Carotid Body / Q000166:cytology / Q000378:metabolism; D015687:Cell Hypoxia; D002628:Chemoreceptor Cells / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000378:metabolism*; D006706:Homeostasis; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015221:Potassium Channels; D000255:Adenosine Triphosphate; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I; C000610360:Ndufs2 protein, mouse; D010100:Oxygen