Copper homeostasis in Drosophila by complex interplay of import, storage and behavioral avoidance.

Copper is an essential but potentially toxic trace element. In Drosophila, the metal-responsive transcription factor (MTF-1) plays a dual role in copper homeostasis: at limiting copper concentrations, it induces the Ctr1B copper importer gene, whereas at high copper concentrations, it mainly induces the metallothionein genes. Here we find that, despite the downregulation of the Ctr1B gene at high copper concentrations, the protein persists on the plasma membrane of intestinal cells for many hours and thereby fills the intracellular copper stores. Drosophila may risk excessive copper accumulation for the potential benefit of overcoming a period of copper scarcity. Indeed, we find that copper-enriched flies donate a vital supply to their offspring, allowing the following generation to thrive on low-copper food. We also describe two additional modes of copper handling: behavioral avoidance of food containing high (>or=0.5 mM) copper levels, as well as the ability of DmATP7, the Drosophila homolog of Wilson/Menkes disease copper exporters, to counteract copper toxicity. Regulated import, storage, export, and avoidance of high-copper food establish an adequate copper homeostasis under variable environmental conditions.