Hypoxia-inducible factor induces cysteine dioxygenase and promotes cysteine homeostasis in Caenorhabditis elegans

Dedicated genetic pathways regulate cysteine homeostasis. For example, high levels of cysteine activate cysteine dioxygenase, a key enzyme in cysteine catabolism in most animal and many fungal species. The mechanism by which cysteine dioxygenase is regulated is largely unknown. In an unbiased genetic screen for mutations that activate cysteine dioxygenase (cdo-1) in the nematode C. elegans, we isolated loss-of-function mutations in rhy-1 and egl-9, which encode proteins that negatively regulate the stability or activity of the oxygen-sensing hypoxia-inducible transcription factor (hif-1). EGL-9 and HIF-1 are core members of the conserved eukaryotic hypoxia response. However, we demonstrate that the mechanism of HIF-1-mediated induction of cdo-1 is largely independent of EGL-9 prolyl hydroxylase activity and the von Hippel-Lindau E3 ubiquitin ligase, the classical hypoxia signaling pathway components. We demonstrate that C. elegans cdo-1 is transcriptionally activated by high levels of c..., All data is from fluorescence microscopy, C. elegans growth assays, or C. elegans survival assays., , # Hypoxia-inducible factor induces cysteine dioxygenase and promotes cysteine homeostasis in *Caenorhabditis elegans*

All data is from fluorescence microscopy, *C. elegans* growth assays, or *C. elegans* survival assays.

## Description of the data and file structure

Figures 1E, 2B, 2C, 3B, 3C, and 5D represent Pcdo-1::GFP expression in *C. elegans*. Data are lists of mean GFP fluorescent values in a defined region of interest. Quantification was performed in FIJI and values are reported in arbitrary units. Genotypes and experimental conditions are displayed when appropriate.

Figure 4- figure supplements 1B and 2B represent CDO-1::GFP expression in *C. elegans*. Data are lists of mean GFP fluorescent values in a defined region of interest. Quantification was performed in FIJI and values are reported in arbitrary units. Genotypes and experimental conditions are displayed when appropriate.

Figures 4C, 4D, and Figure 1- figure supplement 1 represent the quantification of animal lengt...