RT Journal Article
T1 Molecular Mechanisms of Acute Oxygen Sensing by Arterial Chemoreceptor Cells. Role of Hif2α
A1 Ortega-Sáenz, Patricia
A1 Moreno-Domínguez, Alejandro
A1 Gao, Lin
A1 López-Barneo, José
K1 Carotid body
K1 Glomus cells
K1 Acute O2 sensing
K1 Electron transport chain
K1 Mitochondrial signaling
K1 Ion channels
K1 Mechanism of disease
K1 Paraganglioma
K1 Cuerpo carotídeo
K1 Enfermedades mitocondriales
K1 Mitocondrias
K1 Canales iónicos
AB Carotid body glomus cells are multimodal arterial chemoreceptors able to sense and integrate changes in several physical and chemical parameters in the blood. These cells are also essential for O2 homeostasis. Glomus cells are prototypical peripheral O2 sensors necessary to detect hypoxemia and to elicit rapid compensatory responses (hyperventilation and sympathetic activation). The mechanisms underlying acute O2 sensing by glomus cells have been elusive. Using a combination of mouse genetics and single-cell optical and electrophysiological techniques, it has recently been shown that activation of glomus cells by hypoxia relies on the generation of mitochondrial signals (NADH and reactive oxygen species), which modulate membrane ion channels to induce depolarization, Ca2+ influx, and transmitter release. The special sensitivity of glomus cell mitochondria to changes in O2 tension is due to Hif2α-dependent expression of several atypical mitochondrial subunits, which are responsible for an accelerated oxidative metabolism and the strict dependence of mitochondrial complex IV activity on O2 availability. A mitochondrial-to-membrane signaling model of acute O2 sensing has been proposed, which explains existing data and provides a solid foundation for future experimental tests. This model has also unraveled new molecular targets for pharmacological modulation of carotid body activity potentially relevant in the treatment of highly prevalent medical conditions.
PB Frontiers
YR 2020
FD 2020-11-23
LK http://hdl.handle.net/10668/3708
UL http://hdl.handle.net/10668/3708
LA en
NO Ortega-Sáenz P, Moreno-Domínguez A, Gao L, López-Barneo J. Molecular Mechanisms of Acute Oxygen Sensing by Arterial Chemoreceptor Cells. Role of Hif2α. Front Physiol. 2020 Nov 23;11:614893
DS RISalud
RD Apr 10, 2025