Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023:1427:153-162.
doi: 10.1007/978-3-031-32371-3_17.

Constitutive Expression of Hif2α Confers Acute O2 Sensitivity to Carotid Body Glomus Cells

Olalla Colinas  1   2   3 , Alejandro Moreno-Domínguez  1   2   3 , Patricia Ortega-Sáenz  1   2   3 , José López-Barneo  4   5   6
Affiliations

Constitutive Expression of Hif2α Confers Acute O2 Sensitivity to Carotid Body Glomus Cells

Olalla Colinas et al. Adv Exp Med Biol. 2023.

Abstract

Acute oxygen (O2) sensing and adaptation to hypoxia are essential for physiological homeostasis. The prototypical acute O2 sensing organ is the carotid body, which contains chemosensory glomus cells expressing O2-sensitive K+ channels. Inhibition of these channels during hypoxia leads to cell depolarization, transmitter release, and activation of afferent sensory fibers terminating in the brain stem respiratory and autonomic centers. Focusing on recent data, here we discuss the special sensitivity of glomus cell mitochondria to changes in O2 tension due to Hif2α-dependent expression of several atypical mitochondrial electron transport chain subunits and enzymes. These are responsible for an accelerated oxidative metabolism and the strict dependence of mitochondrial complex IV activity on O2 availability. We report that ablation of Epas1 (the gene coding Hif2α) causes a selective downregulation of the atypical mitochondrial genes and a strong inhibition of glomus cell acute responsiveness to hypoxia. Our observations indicate that Hif2α expression is required for the characteristic metabolic profile of glomus cells and provide a mechanistic explanation for the acute O2 regulation of breathing.

Keywords: Acute oxygen sensing; Carotid body; Cell physiology; Glomus cells; Hypoxia; Mitochondrial subunit isoforms.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aras S, Pak O, Sommer N, Finley R Jr, Huttemann M, Weissmann N, Grossman LI (2013) Oxygen-dependent expression of cytochrome c oxidase subunit 4-2 gene expression is mediated by transcription factors RBPJ, CXXC5 and CHCHD2. Nucleic Acids Res 41(4):2255–2266 - PubMed - PMC - DOI
    1. Arias-Mayenco I, Gonzalez-Rodriguez P, Torres-Torrelo H, Gao L, Fernandez-Aguera MC, Bonilla-Henao V, Ortega-Saenz P, Lopez-Barneo J (2018) Acute O2 sensing: role of coenzyme QH2/Q ratio and mitochondrial ROS compartmentalization. Cell Metab 28(1):145–158 e144 - PubMed - DOI
    1. Balsa E, Marco R, Perales-Clemente E, Szklarczyk R, Calvo E, Landazuri MO et al (2012) NDUFA4 is a subunit of complex IV of the mammalian electron transport chain. Cell Metab 16:378–386 - PubMed - DOI
    1. Brown ST, Kelly KF, Daniel JM, Nurse CA (2009) Hypoxia inducible factor (HIF)-2 alpha is required for the development of the catecholaminergic phenotype of sympathoadrenal cells. J Neurochem 110(2):622–630 - PubMed - DOI
    1. Buckler KJ (2015) TASK channels in arterial chemoreceptors and their role in oxygen and acid sensing. Pflugers Arch 467(5):1013–1025 - PubMed - PMC - DOI

LinkOut - more resources