Artículo
Oxygen regulation of breathing is abolished in mitochondrial complex III-deficient arterial chemoreceptors
Autor/es | Cabello Rivera, Daniel
Ortega Sáenz, Patricia Gao Chen, Lin Muñoz Cabello, Ana María Bonilla-Henao, Victoria Schumacker, Paul T. López Barneo, José |
Departamento | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
Fecha de publicación | 2022 |
Fecha de depósito | 2023-12-27 |
Publicado en |
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Resumen | 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 ... 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. |
Agencias financiadoras | Andalusian Government Spanish Ministries of Science and Innovation and Health European Research Council (ERC) |
Identificador del proyecto | US-1255654
SAF2016-74990-R PID2019-106410RB-I00 PRJ201502629 |
Cita | Cabello Rivera, D., Ortega Sáenz, P., Gao Chen, L., Muñoz Cabello, A.M., Bonilla-Henao, V., Schumacker, P.T. y López Barneo, J. (2022). Oxygen regulation of breathing is abolished in mitochondrial complex III-deficient arterial chemoreceptors. Proceedings of the National Academy of Sciences of the United States of America, 119 (39), e2202178119. https://doi.org/10.1073/pnas.2202178119. |
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pnas 2022 Sep 27;119 issue 39 ... | 2.359Mb | [PDF] | Ver/ | |