Acute O2 Sensing: Role of Coenzyme QH2/Q Ratio and Mitochondrial ROS Compartmentalization

Publication date: Available online 7 June 2018
Source:Cell Metabolism
Author(s): Ignacio Arias-Mayenco, Patricia González-Rodríguez, Hortensia Torres-Torrelo, Lin Gao, M. Carmen Fernández-Agüera, Victoria Bonilla-Henao, Patricia Ortega-Sáenz, José López-Barneo
Acute O2 sensing by peripheral chemoreceptors is essential for mammalian homeostasis. Carotid body glomus cells contain O2-sensitive ion channels, which trigger fast adaptive cardiorespiratory reflexes in response to hypoxia. O2-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 O2 sensing. Our results suggest that acute responsiveness to hypoxia depends on coenzyme QH2/Q ratio-controlled ROS production in MCI.

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Teaser

Arias-Mayenco et al. observe that an inducible deficiency of mitochondrial complex I (MCI) leads to a parallel decrease of carotid body chemoreceptor cell responsiveness to hypoxia. Acute O2 sensing depends on a high CoQH2/CoQ ratio, NADH accumulation, and compartmentalized reactive oxygen species production at MCI to signal membrane ion channel activity.


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