Anthranilate fluorescence marks a calcium-propagated necrotic wave that promotes organismal death in C. elegans.

For cells the passage from life to death can involve a regulated, programmed transition. In contrast to cell death, the mechanisms of systemic collapse underlying organismal death remain poorly understood. Here we present evidence of a cascade of cell death involving the calpain-cathepsin necrosis pathway that can drive organismal death in Caenorhabditis elegans. We report that organismal death is accompanied by a burst of intense blue fluorescence, generated within intestinal cells by the necrotic cell death pathway. Such death fluorescence marks an anterior to posterior wave of intestinal cell death that is accompanied by cytosolic acidosis. This wave is propagated via the innexin INX-16, likely by calcium influx. Notably, inhibition of systemic necrosis can delay stress-induced death. We also identify the source of the blue fluorescence, initially present in intestinal lysosome-related organelles (gut granules), as anthranilic acid glucosyl esters--not, as previously surmised, the damage product lipofuscin. Anthranilic acid is derived from tryptophan by action of the kynurenine pathway. These findings reveal a central mechanism of organismal death in C. elegans that is related to necrotic propagation in mammals--e.g., in excitotoxicity and ischemia-induced neurodegeneration. Endogenous anthranilate fluorescence renders visible the spatio-temporal dynamics of C. elegans organismal death.

The mysterious case of the C. elegans gut granule: death fluorescence, anthranilic acid and the kynurenine pathway.

Gut granules are lysosome-like organelles with acidic interiors that are found in large numbers within the intestine of the nematode Caenorhabditis elegans. They are particularly prominent when viewed under ultraviolet light, which causes them to emit intense blue fluorescence. Yet the function of these large and abundant organelles in this heavily-studied model organism remains unclear. One possibility is that they serve as storage organelles, for example of zinc. A new clue to gut granule function is the identification of the blue fluorescent material that they contain as a glycosylated form of anthranilic acid, which is derived from tryptophan by action of the kynurenine pathway. This compound can also serve a surprising role as a natural, endogenous marker of organismal death.