A conceptual framework is offered for critically approaching the formidable ability of insects to segregate metal ions to their multiple destinations in proteins and subcellular compartments. New research in Drosophila melanogaster suggests that nuclear iron regulatory proteins and oxidative stress transcription factors mediate metal-responsive gene expression. Identification of a zinc-regulated chaperone in the endoplasmic reticulum potentially explains membrane protein trafficking defects observed in zinc transporter mutants. Compartmentalized zinc is utilized in fertilization, embryogenesis and for the activation of zinc-finger transcription factors - the latter function demonstrated during muscle development, while dietary zinc is sensed through gating of a chloride channel. Another emerging theme in cellular metal homeostasis is that transporters and related proteins meet at endoplasmic reticulum-mitochondria associated membranes with physiologically relevant consequences during aging.
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