O₂ sensing is essential for mammalian homeostasis. Peripheral chemoreceptors such as the carotid body (CB) contain cells with O₂-sensitive K⁺ channels, which are inhibited by hypoxia to trigger fast adaptive cardiorespiratory reflexes.

How variations of O₂ tension (PO₂) are detected and the mechanisms whereby these changes are conveyed to membrane ion channels have remained elusive.

Researchers have studied acute O₂ sensing in conditional knockout mice lacking mitochondrial complex I (MCI) genes. They 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.

These 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.

http://www.cell.com/cell-metabolism/abstract/S1550-4131(15)00461-1