Abstract
Hypoxia resulting from reduced oxygen (O (2)) levels in the arterial blood is sensed by the carotid body (CB) and triggers reflex stimulation of breathing and blood pressure to maintain homeostasis. Studies in the past five years provided novel insights into the roles of heme oxygenase-2 (HO-2), a carbon monoxide (CO)-producing enzyme, and NADH dehydrogenase Fe-S protein 2, a subunit of the mitochondrial complex I, in hypoxic sensing by the CB. HO-2 is expressed in type I cells, the primary O2-sensing cells of the CB, and binds to O (2) with low affinity. O (2)-dependent CO production from HO-2 mediates hypoxic response of the CB by regulating H (2)S generation. Mice lacking NDUFS2 show that complex I-generated reactive oxygen species acting on K (+) channels confer type I cell response to hypoxia. Whether these signaling pathways operate synergistically or independently remains to be studied.