Hypoxia sensing requires H2S-dependent persulfidation of olfactory receptor 78

Jie Peng, Ying-Jie; Nanduri, Jayasri; Wang, Ning; Kumar, Ganesh K.; Bindokas, Vytautas; Paul, Bindu D.; Chen, Xuanmao; Fox, Aaron P.; Vignane, Thibaut; Filipovic, Milos R.; Prabhakar, Nanduri R.

doi:10.6082/t2pe8-7hm87

Published July 7, 2023 | Version v1

Journal article Open

Hypoxia sensing requires H2S-dependent persulfidation of olfactory receptor 78

1. University of Chicago
2. Johns Hopkins University
3. University of New Hampshire
4. Leibniz-Institut für Analytische Wissenschaften–ISAS

Oxygen (O₂) sensing by the carotid body is critical for maintaining cardiorespiratory homeostasis during hypoxia. Hydrogen sulfide (H₂S) signaling is implicated in carotid body activation by low O₂. Here, we show that persulfidation of olfactory receptor 78 (Olfr78) by H₂S is an integral component of carotid body activation by hypoxia. Hypoxia and H₂S increased persulfidation in carotid body glomus cells and persulfidated cysteine²⁴⁰ in Olfr78 protein in heterologous system. Olfr78 mutants manifest impaired carotid body sensory nerve, glomus cell, and breathing responses to H₂S and hypoxia. Glomus cells are positive for GOlf, adenylate cyclase 3 (Adcy3) and cyclic nucleotide–gated channel alpha 2 (Cnga2), key molecules of odorant receptor signaling. Adcy3 or Cnga2 mutants exhibited impaired carotid body and glomus cell responses to H₂S and breathing responses to hypoxia. These results suggest that H₂S through redox modification of Olfr78 participates in carotid body activation by hypoxia to regulate breathing.

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All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.

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