Long-lived cells, including stem cells and cancer stem cells, often reside in a low oxygen (hypoxic) niche. Accumulating evidence suggests that the activation of genetic programs by hypoxia-inducible factor 1 (HIF-1) is important for growth, survival, and the self-renewal capability of these cells. C. elegans uses simple diffusion for gas exchange, allowing us to both deliver precise amounts of oxygen to all cells in the organism and study the effects of hypoxia on different cell types. In wild-type animals, development and reproduction continue when animals are exposed to 0.5% O2. In contrast, we have found that loss of function mutations in either
hif-1 or
aak-2, the catalytic subunit of AMP-activated protein kinase (AMPK), cause a reversible arrest of cell divisions and postembryonic development in larvae, and reproductive development ceases in adults. Our data indicate that AMPK and HIF-1 act in different pathways to regulate developmental arrest in hypoxia. Activating AMPK by metformin in a
hif-1 mutant was not sufficient to sustain reproductive activity in 0.5% O2, and developmental arrest was not perturbed in a
vhl-1 (
ok161);
aak-2(
ok524) strain. Through an EMS screen, we isolated lines that exhibit perturbed development in hypoxia. The identification of the causative genetic lesions in these strains will provide insight into the genetic pathways responsible for promoting C. elegans development in hypoxia and may offer insight into what long-lived cells require in order to survive. .