Oxygen regulation of breathing is abolished in mitochondrial complex III-deficient arterial chemoreceptors.

Autor:	Cabello-Rivera D; Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Seville, 41013 Spain.; Department of Medical Physiology and Biophysics, University of Seville Medical School, 41009 Seville, Spain.; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, 28031 Madrid, Spain., Ortega-Sáenz P; Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Seville, 41013 Spain.; Department of Medical Physiology and Biophysics, University of Seville Medical School, 41009 Seville, Spain.; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, 28031 Madrid, Spain., Gao L; Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Seville, 41013 Spain.; Department of Medical Physiology and Biophysics, University of Seville Medical School, 41009 Seville, Spain.; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, 28031 Madrid, Spain., Muñoz-Cabello AM; Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Seville, 41013 Spain.; Department of Medical Physiology and Biophysics, University of Seville Medical School, 41009 Seville, Spain.; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, 28031 Madrid, Spain., Bonilla-Henao V; Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Seville, 41013 Spain.; Department of Medical Physiology and Biophysics, University of Seville Medical School, 41009 Seville, Spain.; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, 28031 Madrid, Spain., Schumacker PT; Department of Pediatrics, Northwestern University, Chicago, IL 60611., López-Barneo J; Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Científicas, Universidad de Sevilla, Seville, 41013 Spain.; Department of Medical Physiology and Biophysics, University of Seville Medical School, 41009 Seville, Spain.; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, 28031 Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Sep 27; Vol. 119 (39), pp. e2202178119. Date of Electronic Publication: 2022 Sep 19.
DOI:	10.1073/pnas.2202178119
Abstrakt:	Acute oxygen (O 2 ) sensing is essential for adaptation of organisms to hypoxic environments or medical conditions with restricted exchange of gases in the lung. The main acute O 2 -sensing organ is the carotid body (CB), which contains neurosecretory chemoreceptor (glomus) cells innervated by sensory fibers whose activation by hypoxia elicits hyperventilation and increased cardiac output. Glomus cells have mitochondria with specialized metabolic and electron transport chain (ETC) properties. Reduced mitochondrial complex (MC) IV activity by hypoxia leads to production of signaling molecules (NADH and reactive O 2 species) in MCI and MCIII that modulate membrane ion channel activity. We studied mice with conditional genetic ablation of MCIII that disrupts the ETC in the CB and other catecholaminergic tissues. Glomus cells survived MCIII dysfunction but showed selective abolition of responsiveness to hypoxia (increased [Ca 2+ ] and transmitter release) with normal responses to other stimuli. Mitochondrial hypoxic NADH and reactive O 2 species signals were also suppressed. MCIII-deficient mice exhibited strong inhibition of the hypoxic ventilatory response and altered acclimatization to sustained hypoxia. These data indicate that a functional ETC, with coupling between MCI and MCIV, is required for acute O 2 sensing. O 2 regulation of breathing results from the integrated action of mitochondrial ETC complexes in arterial chemoreceptors.
Databáze:	MEDLINE
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