Necrotic death of cells in response to cellular insult can be executed in different ways. In
Caenorhabditis elegans excess nicotinamide (NAM) causes necrotic death of uterine vulval uv1
cells and OLQ mechanosensory neurons. This effect was first observed in NAD+ deficient pnc-1
salvage mutants. This study aimed to understand if death in these two cell types follows previously
characterized cell death models or differs in their underlying mechanism. Choosing the best-studied
mec-4d induced touch cell necrosis as our model we showed that necrosis of the uv1 and OLQ cell
in our pnc-1 model are different from mec-4d and from each other. Our findings confirmed that
although uv1 cell necrosis requires calpain and aspartic proteases like touch cell necrosis, it is
independent of changes in the intracellular calcium levels and autophagy pathway. OLQ necrosis
does not require changes in the intracellular calcium level, calpain, and aspartic protease activity
or involvement of the autophagy pathway. Instead, OLQ survival is exacerbated when endoplasmic
reticulum calcium-binding proteins calnexin, calreticulin, or axon guidance protein UNC-14
activity is lost. Based on these findings we propose that although touch cell, uv1, and OLQ cell
death share morphological resemblance they are executed by discrete molecular mechanisms.
