Oxygen regulation of breathing is abolished in mitochondrial complex III-deficient arterial chemoreceptors
| Autor: | Daniel Cabello-Rivera, Patricia Ortega-Sáenz, Lin Gao, Ana M. Muñoz-Cabello, Victoria Bonilla-Henao, Paul T. Schumacker, José López-Barneo |
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| Přispěvatelé: | Junta de Andalucía, European Commission, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Research Council, Ministerio de Educación, Cultura y Deporte (España) |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Mitochondrial O2 sensing and signaling
Carotid body glomus cell Multidisciplinary hypoxia Mitochondrial complex III Respiration acute O2 sensing Acute O2 sensing NAD mitochondrial O2 sensing and signaling Cell Hypoxia Ion Channels Oxygen Electron Transport Complex III Mice mitochondrial complex III carotid body glomus cell Animals Hypoxia |
| Popis: | Acute oxygen (O2) sensing is essential for adaptation of organisms to hypoxic environments or medical conditions with restricted exchange of gases in the lung. The main acute O2-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 O2 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 [Ca2+] and transmitter release) with normal responses to other stimuli. Mitochondrial hypoxic NADH and reactive O2 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 O2 sensing. O2 regulation of breathing results from the integrated action of mitochondrial ETC complexes in arterial chemoreceptors. This research was supported by the Andalusian Government (Fondos Feder US-1255654), Spanish Ministries of Science and Innovation and Health (Grants SAF2016-74990-R and PID2019-106410RB-I00 funded by MCIN/AEI/10.13039/501100011033), and the European Research Council (ERC Advanced Grant PRJ201502629). D.C.-R. received a predoctoral fellowship (FPU program) from the Spanish Government. |
| Databáze: | OpenAIRE |
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