Cell Metab. 15, 88–99 (2012)

Myriad cellular processes depend on zinc, and organisms require homeostatic mechanisms to regulate this metal. Although zinc storage organelles have been identified in eukaryotic cells, how cellular storage contributes to homeostasis at the organismal level remains unclear. To investigate this question, Roh et al. used the zinc-specific fluorescent dye FluoZin-3 and lysosome-specific markers in Caenorhabditis elegans to show that zinc was concentrated in gut granules in intestinal cells and that the level of labile zinc in these granules responded to the concentration of dietary zinc. Mutation of glo genes important for lysosome biogenesis or of the gene encoding the cation diffusion facilitator protein cdf-2, which concentrates zinc in organelles, reduced zinc content in both the gut granules and the entire worm. The relative growth of wild-type worms or glo- or cdf-2 –mutant worms in response to dietary zinc supplementation, but not that of other metals, suggested that the gut granules may have a role during zinc toxicity. Zinc deficiency similarly coincided with a loss of FluoZin-3 signal from gut granules. Under zinc-deficient conditions, worms pre-fed zinc showed a growth advantage over those that were not presupplemented, and mutation of cdf-2 abrogated this advantage. Together, these data suggest that worms depend on cdf-2 to store excess labile zinc in lysosome-related organelles in intestinal cells and that these stores can be mobilized during dietary deficiency.