Metal ions : cellular pilgrimages

Metal ions need to be recovered from the environment, where they accumulate, by cells. Current research in this field is very actively concerned with the questions of how a given metal ion is solubilized, how it crosses membranes, accesses the right cellular compartment and is addressed to the right protein where it must selectively bind. These issues were discussed using copper metabolism as a model, involving intracellular metallochaperones whose function is to protect and guide metal ions through the cytoplasm to their protein targets, to which they deliver their ions. In the case of copper, which is a toxic metal when free in solution, there is an absolute necessity to keep the cellular concentration of free copper very low. Metallochaperones involved in copper transport - notably to supply an antioxidant enzyme such as superoxide dismutase, or membrane copper ATPases whose mutations are responsible for genetic diseases (Wilson's disease and Menkès disease) - were more particularly discussed from the point of view of their three-dimensional structures, their copper binding modes and their copper transfer mechanisms to protein targets.