Molecular Mechanisms of Acute Oxygen Sensing by Arterial Chemoreceptor Cells. Role of Hif2α

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 e...

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Detalles Bibliográficos
Autores: Ortega-Sáenz, Patricia, Moreno-Domínguez, Alejandro, Gao, Lin, López-Barneo, José
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/236522
Acceso en línea:http://hdl.handle.net/10261/236522
Access Level:acceso abierto
Palabra clave:Carotid body
Glomus cells
Acute O2 sensing
Electron transport chain
Mitochondrial signaling
Ion channels
Mechanisms of disease
Paraganglioma
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spelling Molecular Mechanisms of Acute Oxygen Sensing by Arterial Chemoreceptor Cells. Role of Hif2αOrtega-Sáenz, PatriciaMoreno-Domínguez, AlejandroGao, LinLópez-Barneo, JoséCarotid bodyGlomus cellsAcute O2 sensingElectron transport chainMitochondrial signalingIon channelsMechanisms of diseaseParagangliomaCarotid 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.This research was supported by the Spanish Ministries of Science and Innovation and Health (SAF2012-39343 and SAF2016-74990-R) and the European Research Council (ERC-ADGPRJ201502629).Frontiers MediaMinisterio de Economía y Competitividad (España)European Research CouncilConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120202021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_dcae04bcPublisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/236522reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://doi.org/10.3389/fphys.2020.614893Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2365222026-05-22T06:33:51Z
dc.title.none.fl_str_mv Molecular Mechanisms of Acute Oxygen Sensing by Arterial Chemoreceptor Cells. Role of Hif2α
title Molecular Mechanisms of Acute Oxygen Sensing by Arterial Chemoreceptor Cells. Role of Hif2α
spellingShingle Molecular Mechanisms of Acute Oxygen Sensing by Arterial Chemoreceptor Cells. Role of Hif2α
Ortega-Sáenz, Patricia
Carotid body
Glomus cells
Acute O2 sensing
Electron transport chain
Mitochondrial signaling
Ion channels
Mechanisms of disease
Paraganglioma
title_short Molecular Mechanisms of Acute Oxygen Sensing by Arterial Chemoreceptor Cells. Role of Hif2α
title_full Molecular Mechanisms of Acute Oxygen Sensing by Arterial Chemoreceptor Cells. Role of Hif2α
title_fullStr Molecular Mechanisms of Acute Oxygen Sensing by Arterial Chemoreceptor Cells. Role of Hif2α
title_full_unstemmed Molecular Mechanisms of Acute Oxygen Sensing by Arterial Chemoreceptor Cells. Role of Hif2α
title_sort Molecular Mechanisms of Acute Oxygen Sensing by Arterial Chemoreceptor Cells. Role of Hif2α
dc.creator.none.fl_str_mv Ortega-Sáenz, Patricia
Moreno-Domínguez, Alejandro
Gao, Lin
López-Barneo, José
author Ortega-Sáenz, Patricia
author_facet Ortega-Sáenz, Patricia
Moreno-Domínguez, Alejandro
Gao, Lin
López-Barneo, José
author_role author
author2 Moreno-Domínguez, Alejandro
Gao, Lin
López-Barneo, José
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
European Research Council
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Carotid body
Glomus cells
Acute O2 sensing
Electron transport chain
Mitochondrial signaling
Ion channels
Mechanisms of disease
Paraganglioma
topic Carotid body
Glomus cells
Acute O2 sensing
Electron transport chain
Mitochondrial signaling
Ion channels
Mechanisms of disease
Paraganglioma
description 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.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_dcae04bc
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/236522
url http://hdl.handle.net/10261/236522
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://doi.org/10.3389/fphys.2020.614893
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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