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- Arias-Mayenco 2018 Cell Metab + (Acute O<sub>2</sub> sensing by … Acute O<sub>2</sub> sensing by peripheral chemoreceptors is essential for mammalian homeostasis. Carotid body glomus cells contain O<sub>2</sub>-sensitive ion channels, which trigger fast adaptive cardiorespiratory reflexes in response to hypoxia. O<sub>2</sub>-sensitive cells have unique metabolic characteristics that favor the hypoxic generation of mitochondrial complex I (MCI) signaling molecules, NADH and reactive oxygen species (ROS), which modulate membrane ion channels. We show that responsiveness to hypoxia progressively disappears after inducible deletion of the Ndufs2 gene, which encodes the 49 kDa subunit forming the coenzyme Q binding site in MCI, even in the presence of MCII substrates and chemical NAD+ regeneration. We also show contrasting effects of physiological hypoxia on mitochondrial ROS production (increased in the intermembrane space and decreased in the matrix) and a marked effect of succinate dehydrogenase activity on acute O<sub>2</sub> sensing. Our results suggest that acute responsiveness to hypoxia depends on coenzyme QH2/Q ratio-controlled ROS production in MCI.esponsiveness to hypoxia depends on coenzyme QH2/Q ratio-controlled ROS production in MCI.)
