A delicate balance: Homeostatic control of copper uptake and distribution

The cellular uptake and intracellular distribution of the essential but hig hly toxic nutrient, copper, is a precisely orchestrated process. Copper hom eostasis is coordinated by several proteins to ensure that it is delivered to specific subcellular compartments and copper-requiring proteins without releasing free copper ions that will cause damage to cellular components. G enetic studies in prokaryotic organisms and yeast have identified membrane- associated proteins that mediate the uptake or export of copper from cells. Within cells, small cytosolic proteins, called copper chaperones, have bee n identified that bind copper ions and deliver them to specific compartment s and copper-requiring proteins. The identification of mammalian homologues of these proteins reveal a remarkable structural and functional conservati on of copper metabolism between bacteria, yeast and humans. Furthermore, st udies on the function and localization of the products of the Menkes and Wi lson's disease genes, which are defective in patients afflicted with these diseases, have provided valuable insight into the mechanisms of copper bala nce and their role in maintaining appropriate copper distribution in mammal s.