A model for dietary zinc absorption in Drosophila enterocytes. Dietary zinc absorption takes a direct transversing path through the midgut cells, bypassing the intracellular organelles. Zinc uptake from the lumen involves the Drosophila transporters dZip1 and dZip2 on the apical membrane, and these transporters are negatively affected at the RNA level by zinc in the enterocytes. Cytosolic zinc is pumped out into circulation by dZnT1 and CG5130 on the basolateral membrane. dZnT1 is post-transcriptionally repressed by zinc overload, whereas CG5130 is unresponsive to dietary zinc changes. Zinc in the cytosol is bound by metallothioneins to prevent its toxicity when overloaded. Zinc transporters along the secretion pathway are not directly involved in zinc efflux to the circulation. The regulated expression the zinc transporters mediating dietary zinc uptake depends autonomously on the zinc level in the enterocyte per se, and is unresponsive to the zinc status in the rest of the body. The negative regulation of zinc transporters by dietary zinc occurs through altering the zinc levels in the enterocyte.