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The main acute O\n                    <jats:sub>2<\/jats:sub>\n                    -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\n                    <jats:sub>2<\/jats:sub>\n                    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\n                    <jats:sup>2+<\/jats:sup>\n                    ] and transmitter release) with normal responses to other stimuli. Mitochondrial hypoxic NADH and reactive O\n                    <jats:sub>2<\/jats:sub>\n                    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\n                    <jats:sub>2<\/jats:sub>\n                    sensing. O\n                    <jats:sub>2<\/jats:sub>\n                    regulation of breathing results from the integrated action of mitochondrial ETC complexes in arterial chemoreceptors.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2202178119","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T15:16:45Z","timestamp":1663600605000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":23,"title":["Oxygen regulation of breathing is abolished in mitochondrial complex III-deficient arterial chemoreceptors"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7628-0000","authenticated-orcid":false,"given":"Daniel","family":"Cabello-Rivera","sequence":"first","affiliation":[{"name":"Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Roc\u00edo, Consejo Superior de Investigaciones Cient\u00edficas, Universidad de Sevilla, Seville, 41013 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