Hypoxia sensing requires HS-dependent persulfidation of olfactory receptor 78.

Oxygen (O) sensing by the carotid body is critical for maintaining cardiorespiratory homeostasis during hypoxia. Hydrogen sulfide (HS) signaling is implicated in carotid body activation by low O. Here, we show that persulfidation of olfactory receptor 78 (Olfr78) by HS is an integral component of carotid body activation by hypoxia. Hypoxia and HS increased persulfidation in carotid body glomus cells and persulfidated cysteine in Olfr78 protein in heterologous system. mutants manifest impaired carotid body sensory nerve, glomus cell, and breathing responses to HS and hypoxia. Glomus cells are positive for G adenylate cyclase 3 (Adcy3) and cyclic nucleotide-gated channel alpha 2 (Cnga2), key molecules of odorant receptor signaling. or mutants exhibited impaired carotid body and glomus cell responses to HS and breathing responses to hypoxia. These results suggest that HS through redox modification of Olfr78 participates in carotid body activation by hypoxia to regulate breathing.