Hypoxia sensing requires H<sub>2</sub>S-dependent persulfidation of olfactory receptor 78.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37406126.
- Also identified by DOI 10.1126/sciadv.adf3026 and PMC identifier 10321732.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Oxygen (O<sub>2</sub>) sensing by the carotid body is critical for maintaining cardiorespiratory homeostasis during hypoxia. Hydrogen sulfide (H<sub>2</sub>S) signaling is implicated in carotid body activation by low O<sub>2</sub>. Here, we show that persulfidation of olfactory receptor 78 (Olfr78) by H<sub>2</sub>S is an integral component of carotid body activation by hypoxia. Hypoxia and H<sub>2</sub>S increased persulfidation in carotid body glomus cells and persulfidated cysteine<sup>240</sup> in Olfr78 protein in heterologous system. <i>Olfr78</i> mutants manifest impaired carotid body sensory nerve, glomus cell, and breathing responses to H<sub>2</sub>S and hypoxia. Glomus cells are positive for G<sub>Olf,</sub> adenylate cyclase 3 (Adcy3) and cyclic nucleotide-gated channel alpha 2 (Cnga2), key molecules of odorant receptor signaling. <i>Adcy3</i> or <i>Cnga2</i> mutants exhibited impaired carotid body and glomus cell responses to H<sub>2</sub>S and breathing responses to hypoxia. These results suggest that H<sub>2</sub>S through redox modification of Olfr78 participates in carotid body activation by hypoxia to regulate breathing.
Medical subject headings
- Receptors, Odorant
- Hydrogen Sulfide
- Carotid Body