Transport of nonessential metals across mammalian cell membranes

Abstract

Nonessential metals are opportunistic. They compete with essential metals for binding to various cofactors, receptors, transcription factors, transporters, and other metalloproteins, and in doing so they gain access to various cellular and subcellular compartments, and interfere in the functions of the essential metals. Because of their high chemical reactivities, nonessential metals also interact nonspecifically with a multitude of other cellular ligands, and interfere with many other cellular processes. In general, nonessential metals cross biological membranes by three mechanisms. First, as indicated above, they often compete with endogenous metals for transport on the various metal ion transporters, pumps, and channels. Alternatively, they may form complexes that are then substrates for other ion and organic solute transporters and pumps. A third general mode of transport involves both signal-induced (e.g. receptor-mediated) and constitutive endocytosis of metals ions and metal complexes. In contrast with these mediated transport pathways, simple diffusion appears to play only a minor role in metal transport. Collectively, these permeation pathways allow toxic metals to reach diverse cellular and subcellular targets, but can also be exploited in the design of therapeutic strategies aimed at accelerating the removal of these toxic elements from the body. © Springer-Verlag Berlin Heidelberg 2006.