RT Journal Article
T1 Acute O2 sensing through HIF2α-dependent expression of atypical cytochrome oxidase subunits in arterial chemoreceptors.
A1 Moreno-Dominguez, Alejandro
A1 Ortega-Saenz, Patricia
A1 Gao, Lin
A1 Colinas, Olalla
A1 Garcia-Flores, Paula
A1 Bonilla-Henao, Victoria
A1 Aragones, Julian
A1 Hüttemann, Maik
A1 Grossman, Lawrence I
A1 Weissmann, Norbert
A1 Sommer, Natascha
A1 Lopez-Barneo, Jose
K1 Arteries
K1 Carotid Body
K1 Hypoxia
K1 Mice, Knockout
K1 Mitochondria
K1 Reactive Oxygen Species
K1 Signal Transduction
AB Acute cardiorespiratory responses to O2 deficiency are essential for physiological homeostasis. The prototypical acute O2-sensing organ is the carotid body, which contains glomus cells expressing K+ channels whose inhibition by hypoxia leads to transmitter release and activation of nerve fibers terminating in the brainstem respiratory center. The mechanism by which changes in O2 tension modulate ion channels has remained elusive. Glomus cells express genes encoding HIF2α (Epas1) and atypical mitochondrial subunits at high levels, and mitochondrial NADH and reactive oxygen species (ROS) accumulation during hypoxia provides the signal that regulates ion channels. We report that inactivation of Epas1 in adult mice resulted in selective abolition of glomus cell responsiveness to acute hypoxia and the hypoxic ventilatory response. Epas1 deficiency led to the decreased expression of atypical mitochondrial subunits in the carotid body, and genetic deletion of Cox4i2 mimicked the defective hypoxic responses of Epas1-null mice. These findings provide a mechanistic explanation for the acute O2 regulation of breathing, reveal an unanticipated role of HIF2α, and link acute and chronic adaptive responses to hypoxia.
PB American Association for the Advancement of Science (AAAS)
YR 2020
FD 2020-01-21
LK http://hdl.handle.net/10668/14839
UL http://hdl.handle.net/10668/14839
LA en
NO Moreno-Domínguez A, Ortega-Sáenz P, Gao L, Colinas O, García-Flores P, Bonilla-Henao V, et al. Acute O2 sensing through HIF2α-dependent expression of atypical cytochrome oxidase subunits in arterial chemoreceptors. Sci Signal. 2020 Jan 21;13(615):eaay9452.
DS RISalud
RD Apr 12, 2025