RT Journal Article
T1 Oxygen regulation of breathing is abolished in mitochondrial complex III-deficient arterial chemoreceptors.
A1 Cabello-Rivera, Daniel
A1 Ortega-Sáenz, Patricia
A1 Gao, Lin
A1 Muñoz-Cabello, Ana M
A1 Bonilla-Henao, Victoria
A1 Schumacker, Paul T
A1 López-Barneo, José
K1 acute O2 sensing
K1 carotid body glomus cell
K1 hypoxia
K1 mitochondrial O2 sensing and signaling
K1 mitochondrial complex III
AB 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.
YR 2022
FD 2022-09-19
LK http://hdl.handle.net/10668/19667
UL http://hdl.handle.net/10668/19667
LA en
DS RISalud
RD Apr 19, 2025