Journal
CELL METABOLISM
Volume 22, Issue 5, Pages 825-837Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2015.09.004
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Funding
- Botin Foundation
- Spanish Ministry of Science and Innovation [ISCiii PIE13/0004]
- Spanish Ministry of Health [ISCiii PIE13/0004]
- FPI program
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O-2 sensing is essential for mammalian homeostasis. Peripheral chemoreceptors such as the carotid body (CB) contain cells with O-2-sensitive K+ channels, which are inhibited by hypoxia to trigger fast adaptive cardiorespiratory reflexes. How variations of O-2 tension (PO2) are detected and the mechanisms whereby these changes are conveyed to membrane ion channels have remained elusive. We have studied acute O-2 sensing in conditional knockout mice lacking mitochondrial complex I (MCI) genes. We inactivated Ndufs2, which encodes a protein that participates in ubiquinone binding. Ndufs2-null mice lose the hyperventilatory response to hypoxia, although they respond to hypercapnia. Ndufs2-deficient CB cells have normal functions and ATP content but are insensitive to changes in PO2. Our data suggest that chemoreceptor cells have a specialized succinate-dependent metabolism that induces an MCI state during hypoxia, characterized by the production of reactive oxygen species and accumulation of reduced pyridine nucleotides, which signal neighboring K+ channels.
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