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bioRxiv · 10.1101/2025.11.20.689412

OSM-11 modulates salinity-stress tolerance in Caenorhabditis elegans

Zhang, P.·Xue, B.·Xie, Y.·Li, K.·Yang, H.·Sun, P.·Zhang, L.
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Abstract

Most terrestrial animals exhibit narrow salinity tolerance compared to their marine counterparts. Previous studies identified osm-11 (which encodes a Notch co-ligand) mutations as a driver of hyper-saline tolerance in Caenorhabditis elegans, but mechanistic insights remained unclear. This study employs RNA sequencing and CRISPR/Cas-9 genome editing to demonstrate that osm-11 mutations enhance salinity stress resistance through up-regulation of fatty acid metabolism (acdh-12, acs-17) and cytochrome P450 pathways (ugt-15), while suppressing calcium signaling. Furthermore, we demonstrated that acdh-12 mutation impairs salinity-stress tolerance by activating ferroptosis and mitophagy, accompanied by down-regulated oxidative phosphorylation and up-regulated autophagic pathways. Morphological observations show that mitochondrial fragmentation contributes to wild-type nematode mortality under high salinity, while enlarged lipid droplets in wild-types correlate with reduced {beta}-oxidation gene expression (dhs-28, daf-22), whose knockout disrupts tolerance in mutants. These findings unravel the multi-pathway regulatory network of osm-11-mediated salinity tolerance, providing mechanistic insights for developing protective strategies against environmental salinity stressors impacting animal survival.

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Zhang, P., Xue, B., Xie, Y., Li, K., Yang, H., Sun, P., Zhang, L.. 2025-11-20. OSM-11 modulates salinity-stress tolerance in Caenorhabditis elegans. https://doi.org/10.1101/2025.11.20.689412

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