While all cells require NAD+ for general metabolism, perturbations in biosynthesis of NAD+ can have surprisingly tissue-specific consequences in physiology and development. We use C. elegans to study the role of NAD+ biosynthetic pathways in cell survival. PNC-1 converts nicotinamide (NAM) to nicotinic acid (NA) in the first step of the invertebrate NAD+ salvage pathway. In
pnc-1 mutants, the OLQ neurons, mechanosensory cells involved in head withdrawal and foraging, are sensitized to nutritional conditions and prone to death. OLQ cells die at a low penetrance when grown under normal culture conditions, but OLQ death increases significantly on UV-killed E. coli. Neither accumulation of the PNC-1 substrate NAM nor the lack of PNC-1 product NA is sufficient to cause OLQ death, which suggests that both low NAM and normal NA levels are required for survival. OLQ cells die with a stereotypical progression; the dendrites first bleb, then the cytoplasm swells dramatically in a manner characteristic of a necrotic cell, followed by dendrite and cell body clearance. We sought to compare OLQ death to the well-studied degenerin/
mec-4d-induced touch cell necrosis model. We found that loss of calreticulin function, which suppresses degenerin-induced death, significantly increased OLQ death. Two
unc-51/Atg1 alleles, which also suppress degnerin-induced death by blocking autophagy, also increased OLQ death. UNC-51 regulates both autophagy and axon guidance. Knockdown of two other autophagy genes,
bec-1 and
lgg-1, had no effect. However, mutation of
unc-14, an
unc-51 axon guidance partner, also showed increased OLQ death, suggesting that correct axon guidance may be essential for OLQ survival. Finally, we found that
asp-4(lf) allele, a key effector of necrosis, did not affect OLQ death. These results suggest that OLQ death in
pnc-1 animals does not follow a canonical necrosis pathway, yet it is not an apoptotic event, as OLQ death increased in
ced-4;
pnc-1 double mutants. OLQ death offers a model to probe a novel death pathway in a system with powerful genetic and metabolomic tools at hand.