Mechanisms involved in metalloid transport and tolerance acquisition

Toxic metalloids such as arsenic and antimony have always been an integral part of the natural environment. To survive in such a hostile habitat, it i s crucial to develop strategies to exclude toxic substances from the cell a nd to acquire tolerance. Cells remove metalloids from the cytosol either by active efflux or by sequestration in an internal organelle. Controlling th e influx appears to be another way of maintaining a low intracellular metal loid content. Inside the cell. the metalloid can be reduced to a form that is recognised by the expulsion system(s). In addition, metalloid complexati on and compartmentalisation contributes to enhanced cellular tolerance. Fin ally, the presence of metalloids activates transcription of various cellula r defence genes. Metalloid-containing drugs are currently used to treat pro tozoan infections and promyelocytic leukaemia. Since metalloid resistance h ampers efficient treatment. interest in identifying the mechanisms involved in tolerance acquisition has arisen. The possibility of using genetic appr oaches has made the yeast Saccharomyces cerevisiae a compelling model syste m to investigate the basis of metalloid tolerance at a molecular level. Thi s review describes the recent progress made in elucidating the mechanisms i nvolved in metalloid transport and tolerance in yeast and other organisms.