RT Journal Article SR Electronic T1 Acute avoidance of hydrogen sulfide is modulated by external and internal states in C. elegans JF bioRxiv FD Cold Spring Harbor Laboratory SP 2023.10.09.561535 DO 10.1101/2023.10.09.561535 A1 Pu, Longjun A1 Zhao, Lina A1 Wang, Jing A1 Henriksson, Johan A1 Laurent, Patrick A1 Chen, Changchun YR 2023 UL http://biorxiv.org/content/early/2023/10/13/2023.10.09.561535.abstract AB Hydrogen sulfide (H2S) can act as an energy source, a poison and a gasotransmitter in organisms. We used the robust locomotory responses to H2S in Caenorhabditis elegans to delineate the molecular mechanisms governing sensory and adaptive responses to H2S exposure. We found that C. elegans exhibited transiently increased locomotory activity and turning behavior as a strategy to escape the noxious H2S stimulation. The behavioral responses to H2S were modulated by a complex network of signaling pathways, including cyclic GMP signaling in ciliated sensory neurons, calcineurin, nuclear hormone receptors, to the major starvation regulators such as insulin and TGF-β signaling. The response to H2S was substantially affected by the ambient O2 levels and their prior experience in low O2 environments, suggesting an intricate interplay between O2 and H2S sensing mechanisms. Prolonged exposure to H2S robustly evoked H2S detoxification coupled with reduced locomotory response to the subsequent H2S challenges. Intriguingly, the expression of genes involved in iron homeostasis, including ftn-1 and smf-3, was substantially modified in exposure to H2S, implying that labile iron levels are affected by H2S. In support of this, iron supplement significantly bolstered the behavioral response to H2S. In addition, mitochondria, one of the central hubs for H2S metabolism, played a crucial role in adaptive responses to H2S. In summary, our study provides molecular insights into the mechanisms through which C. elegans detects, modulates, and adapts its response to H2S.Competing Interest StatementThe authors have declared no competing interest.