Acute avoidance of hydrogen sulfide is modulated by external and internal states inC. elegans

Hydrogen sulfide (H₂S) can act as an energy source, a poison and a gasotransmitter in organisms. We used the robust locomotory responses to H₂S inCaenorhabditis elegansto delineate the molecular mechanisms governing sensory and adaptive responses to H₂S exposure. We found thatC. elegansexhibited 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 O₂levels and their prior experience in low O₂environments, suggesting an intricate interplay between O₂and 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, includingftn-1andsmf-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 whichC. elegansdetects, modulates, and adapts its response to H₂S.