Tamás M J, Wysocki R
Department of Cell and Molecular Biology/Microbiology, Göteburg University, Sweden.
Curr Genet. 2001 Aug;40(1):2-12. doi: 10.1007/s002940100234.
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.
诸如砷和锑之类的有毒类金属一直是自然环境中不可或缺的一部分。为了在如此恶劣的栖息地中生存，制定将有毒物质排除在细胞外并获得耐受性的策略至关重要。细胞通过主动外排或在内部细胞器中隔离来从细胞质中去除类金属。控制摄入似乎是维持低细胞内类金属含量的另一种方式。在细胞内部，类金属可以被还原为可被排出系统识别的形式。此外，类金属络合和区室化有助于增强细胞耐受性。最后，类金属的存在会激活各种细胞防御基因的转录。含类金属的药物目前用于治疗原生动物感染和早幼粒细胞白血病。由于类金属抗性阻碍了有效治疗，人们对确定获得耐受性所涉及的机制产生了兴趣。使用遗传方法的可能性使酿酒酵母成为在分子水平上研究类金属耐受性基础的极具吸引力的模型系统。本综述描述了在阐明酵母和其他生物体中类金属转运和耐受性所涉及的机制方面取得的最新进展。
