Living organisms require oxygen to maintain their lives, however both excess and shortage of oxygen can be stressors to organisms depending on their biological context. Under anoxic conditions (i.e. completely deprived of oxygen), nematodes apparently decrease metabolism rate and arrest cell cycle. However, signaling pathways that regulate survival under anoxic conditions have not been elucidated. Apoptosis signal-regulating kinase (ASK) family proteins are MAP3Ks which activate the
p38 and JNK pathways, and play pivotal roles in responses to stress such as oxidative stress in mammals. C. elegans possesses a single ASK family protein, named NSY-1, and its functions are well conserved with those of mammalian ASK1. Previous reports have shown that
nsy-1 loss-of-function mutation causes decrease in survival rates under oxidative stress and bacterial infection. Here we show that loss-of-function mutation of
nsy-1 increases survival rate under anoxic conditions. When animals were subjected to anoxic conditions (<0.2 % O2),
nsy-1 mutant animals showed higher survival rates than wild type ones. Mutant animals of the components of the
p38 pathways, but not those of JNK pathways, showed higher survival rates. Consistent with these findings, we found that PMK-1, a
p38 MAPK ortholog, was activated in response to anoxia and that the PMK-1 activation in response to anoxia was suppressed in
nsy-1 mutants. These results suggest that the NSY-1-PMK-1 pathway plays important roles in anoxic responses in C. elegans. Exogenous expression of NSY-1 in either of the hypodermal, intestinal, or neuronal tissue suppressed the increase in survival rate under anoxic conditions in
nsy-1 mutants, suggesting the non-cell autonomous roles of NSY-1.