Iron-homeostasis regulation by neuronal oxygen sensors in the nematode Caenorhabditis elegans

Iron presents cells with a double-edged sword. On the one hand, iron is crucial for fundamental physiological processes such as DNA synthesis, oxygen (O 2 ) transport, and mitochondrial respiration. On the other hand, iron can catalyze the formation of toxic oxygen radicals that can destroy any biological molecule. Therefore, it is crucial to understand how the concentration of labile iron is regulated at the whole animal level. And, in particular, how it is controlled in stress conditions in which the level of reactive oxygen species (ROS) is high. Here, we characterized the changes in intestinal gene expression occurring during the adaptation of C. elegans worms to hypoxia and reoxygenation stress. Among the 770 genes that were differentially expressed, the iron storage ferritin 1 (ftn-1) gene was significantly upregulated in hypoxia. Intriguingly, we show that this upregulation is controlled by neuronal oxygen-sensors in a HIF-1-dependent manner. Moreover, our data suggest that FTN-1 plays an important role in innate immunity in hypoxia. These data may provide novel insights about the way iron level is regulated in tumor development where cells may experience mild to severe hypoxia conditions.