SEMI ‐1, A Novel Neuronal Selenium‐Binding Protein 1 Homolog Without Methanethiol Oxidase Activity, Modulates Stress Resistance, Lifespan, and Thermotaxis in C. elegans

Human selenium‐binding protein 1 (SELENBP1) catalyzes the oxidation of the gaseous methionine degradation product, methanethiol. We previously identified a Caenorhabditis elegans ortholog, SEMO‐1, that has the same methanethiol oxidase (MTO) activity. Here, we report the identification and functional characterization of another C. elegans ortholog of human SELENBP1, SEMI‐1. In contrast to SELENBP1 and SEMO‐1, SEMI‐1 (SELENBP1‐homolog, MTO inactive) lacks MTO activity. Notably, semi‐1 expression is confined to thermosensory AFD (amphid finger‐like endings D) and oxygen‐sensing BAG (bag‐like dendritic ending) neurons, as demonstrated using a SEMI‐1::GFP reporter. Depletion of SEMI‐1 results in increased lifespan, improved physiological parameters (motility, progeny), and reduced accumulation of age pigments during aging. SEMI‐1‐deficient nematodes are more resistant to the redox cycler paraquat than wild‐type worms. On the other hand, they show enhanced susceptibility to selenite exposure, indicating a role for SEMI‐1 in conferring selective stress resistance. We also show that SEMI‐1 deficiency is associated with impaired thermotaxis in C. elegans , which is consistent with the role of AFD neurons in thermosensation. In conclusion, SEMI‐1 is a neuronal SELENBP1 ortholog in C. elegans that lacks MTO activity and impairs oxidative stress resistance and shortens lifespan. As a trade‐off, it contributes to C. elegans selenite resistance and thermotaxis. The observed phenotypes of SEMI‐1 deficiency suggest the existence of MTO‐independent effects of other SELENBP1 homologs.