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 is crucial to develop strategies to exclude toxic substances from the cell and to acquire tolerance. Cells remove metalloids from the cytosol either by active efflux or by sequestration in an internal organelle. Controlling the influx appears to be another way of maintaining a low intracellular metalloid content. Inside the cell, the metalloid can be reduced to a form that is recognised by the expulsion system(s). In addition, metalloid complexation and compartmentalisation contributes to enhanced cellular tolerance. Finally, the presence of metalloids activates transcription of various cellular defence genes. Metalloid-containing drugs are currently used to treat protozoan infections and promyelocytic leukaemia. Since metalloid resistance hampers efficient treatment, interest in identifying the mechanisms involved in tolerance acquisition has arisen. The possibility of using genetic approaches has made the yeast Saccharomyces cerevisiae a compelling model system to investigate the basis of metalloid tolerance at a molecular level. This review describes the recent progress made in elucidating the mechanisms involved in metalloid transport and tolerance in yeast and other organisms.
Tamás
M J
MJ
Department of Cell and Molecular Biology/Microbiology, Göteburg University, Sweden. markus.tamas@gmm.gu.se
Wysocki
R
R
D000818:Animals; D000965:Antimony / Q000493:pharmacokinetics* / Q000633:toxicity*; D001151:Arsenic / Q000493:pharmacokinetics* / Q000633:toxicity*; D001693:Biological Transport, Active; D024881:Drug Resistance, Bacterial; D025141:Drug Resistance, Fungal; D004361:Drug Tolerance; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005978:Glutathione; D006801:Humans; D007891:Leishmania / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008667:Metalloproteins / Q000378:metabolism; D008668:Metallothionein / Q000378:metabolism; D009348:Nematoda / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D054811:Phytochelatins; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013559:Symbiosis; D014345:Trypanosoma / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D008667:Metalloproteins; D008668:Metallothionein; D054811:Phytochelatins; D000965:Antimony; D005978:Glutathione; D001151:Arsenic