Mitochondrial Redox Signaling in O2-Sensing Chemoreceptor Cells.

Significance: Acute responses to hypoxia are essential for the survival of mammals. The carotid body (CB), the main arterial chemoreceptor, contains glomus cells with oxygen (O2)-sensitive K+ channels, which are inhibited during hypoxia to trigger adaptive cardiorespiratory reflexes. Recent Advances: In this review, recent advances in molecular mechanisms of acute O2 sensing in CB glomus cells are discussed, with a special focus on the signaling role of mitochondria through regulating cellular redox status. These advances have been achieved thanks to the use of genetically engineered redox-sensitive green fluorescent protein (roGFP) probes, which allowed us to monitor rapid changes in ROS production in real time in different subcellular compartments during hypoxia. This methodology was used in combination with conditional knockout mice models, pharmacological approaches, and transcriptomic studies. We have proposed a mitochondria-to-membrane signaling model of acute O2 sensing in which H2O2 released in the mitochondrial intermembrane space serves as a signaling molecule to inhibit K+ channels on the plasma membrane. Critical Issues: Changes in mitochondrial reactive oxygen species (ROS) production during acute hypoxia are highly compartmentalized in the submitochondrial regions. The use of redox-sensitive probes targeted to specific compartments is essential to fully understand the role of mitochondrial ROS in acute O2 sensing. Future Directions: Further studies are needed to specify the ROS and to characterize the target(s) of ROS in chemoreceptor cells during acute hypoxia. These data may also contribute to a more complete understanding of the implication of ROS in acute responses to hypoxia in O2-sensing cells in other organs. Antioxid. Redox Signal. 37, 274-289.

Citation

Lin Gao, Patricia Ortega-Sáenz, Alejandro Moreno-Domínguez, José López-Barneo. Mitochondrial Redox Signaling in O2-Sensing Chemoreceptor Cells. Antioxidants & redox signaling. 2022 Aug;37(4-6):274-289

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PMID: 35044243

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