Temperature is an important environmental factor that impacts the biochemistry of the organism, with critical consequences to membrane fluidity. Animals respond to changes in ambient temperature through behavior and altered physiology. Better understanding of how animals respond to cold is important for safe and optimal use of cold conditions on live organisms and samples, and for the development of treatments for hypothermia. However, how multicellular organisms sense cold temperature stress and how this leads to habituation to low temperature is poorly understood.

In this study, we demonstrate a role for the ER stress sensor IRE-1 in cold stress resistance in C. elegans. Specifically, we find that IRE-1 is activated by cold and that animals lacking ire-1 display increased sensitivity to extreme cold shock. Interestingly, IRE-1-mediated cold resistance is independent of its luminal domain, which is required for sensing misfolded proteins in the ER lumen. Furthermore, IRE-1-mediated cold resistance relies on JNK-1 signaling rather than on the transcription factor XBP-1.

Strikingly, although the entire animal is exposed to the cold, expression of IRE-1 in a few specific neurons is sufficient to rescue cold stress resistance through a cell-nonautonomous mechanism. Our findings indicate that neuronal IRE-1 regulates lipid composition in the entire animal by regulating neuropeptide-mediated signaling. Altogether, our findings point toward an IRE-1-controlled neuronal signal which controls cold adaptation in the whole organism.