Oxygen Sensing by Arterial Chemoreceptors Depends on Mitochondrial Complex I Signaling

• DOI: 10.1016/j.cmet.2015.09.004
• Publication Date: 2015-10-03T22:20:02Z
• Authors: M. Carmen Fernánd...; Lin Gao; Patricia González...; C. Oscar Pintado; Ignacio Arias-May...; Paula García-Flores; Antonio García-Pe...; Alberto Pascual; Patricia Ortega-S...; José López-Barneo
• Keywords: Mice, Knockout; Carotid Body; 0303 health sciences; Electron Transport Complex I; Potassium Channels; Physiology; NADH Dehydrogenase; Cell Biology; Cell Hypoxia; Chemoreceptor Cells; Mitochondria; 3. Good health; Oxygen; Mice; 03 medical and health sciences; Adenosine Triphosphate; Animals; Homeostasis; Molecular Biology; Signal Transduction

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. We have studied acute O2 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.