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Title: Molecular Mechanisms of Acute Oxygen Sensing by Arterial Chemoreceptor Cells. Role of Hif2α
Authors: Ortega-Sáenz, Patricia
Moreno-Domínguez, Alejandro
Gao, Lin
López-Barneo, José
metadata.dc.contributor.authoraffiliation: [Ortega-Sáenz,P; Moreno-Domínguez,A; Gao,L; López-Barneo,J] Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain. [Ortega-Sáenz,P; Moreno-Domínguez,A; Gao,L; López-Barneo,J] Departamento de Fisiología Médica y Biofísica, Facultad de Medicina, Universidad de Sevilla, Seville, Spain. [Ortega-Sáenz,P; Gao,L; López-Barneo,J] Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Keywords: Carotid body;Glomus cells;Acute O2 sensing;Electron transport chain;Mitochondrial signaling;Ion channels;Mechanism of disease;Paraganglioma;Cuerpo carotídeo;Enfermedades mitocondriales;Mitocondrias;Canales iónicos
metadata.dc.subject.mesh: Medical Subject Headings::Anatomy::Nervous System::Neurons::Neurons, Afferent::Sensory Receptor Cells::Chemoreceptor Cells::Paraganglia, Nonchromaffin::Carotid Body
Medical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Mitochondrial Diseases
Medical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Mitochondria
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Membrane Transport Proteins::Ion Channels
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Oxygen Compounds::Reactive Oxygen Species
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Respiration::Cell Hypoxia
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Homeostasis
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Oxidative Stress
Issue Date: 23-Nov-2020
Publisher: Frontiers
Citation: Ortega-Sáenz P, Moreno-Domínguez A, Gao L, López-Barneo J. Molecular Mechanisms of Acute Oxygen Sensing by Arterial Chemoreceptor Cells. Role of Hif2α. Front Physiol. 2020 Nov 23;11:614893
Abstract: Carotid body glomus cells are multimodal arterial chemoreceptors able to sense and integrate changes in several physical and chemical parameters in the blood. These cells are also essential for O2 homeostasis. Glomus cells are prototypical peripheral O2 sensors necessary to detect hypoxemia and to elicit rapid compensatory responses (hyperventilation and sympathetic activation). The mechanisms underlying acute O2 sensing by glomus cells have been elusive. Using a combination of mouse genetics and single-cell optical and electrophysiological techniques, it has recently been shown that activation of glomus cells by hypoxia relies on the generation of mitochondrial signals (NADH and reactive oxygen species), which modulate membrane ion channels to induce depolarization, Ca2+ influx, and transmitter release. The special sensitivity of glomus cell mitochondria to changes in O2 tension is due to Hif2α-dependent expression of several atypical mitochondrial subunits, which are responsible for an accelerated oxidative metabolism and the strict dependence of mitochondrial complex IV activity on O2 availability. A mitochondrial-to-membrane signaling model of acute O2 sensing has been proposed, which explains existing data and provides a solid foundation for future experimental tests. This model has also unraveled new molecular targets for pharmacological modulation of carotid body activity potentially relevant in the treatment of highly prevalent medical conditions.
metadata.dc.identifier.doi: 10.3389/fphys.2020.614893
ISSN: 1664-042X (Online)
Appears in Collections:01- Artículos - Hospital Virgen del Rocío
01- Artículos - IBIS. Instituto de Biomedicina de Sevilla

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