MFS transporters required for multidrug/multixenobiotic (MD/MX) resistance in the model yeast: understanding their physiological function through post-genomic approaches.
MFS transporters required for multidrug/multixenobiotic (MD/MX) resistance in the model yeast: understanding their physiological function through post-genomic approaches.
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DOI：
10.3389/fphys.2014.00180
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发表时间：
2014
影响因子：
4
通讯作者：
Sá-Correia I
中科院分区：
文献类型：
--
作者：
Dos Santos SC;Teixeira MC;Dias PJ;Sá-Correia I
多药/多外源耐药（MDR/MXR）是一种具有临床、农业和生物技术意义的普遍现象，其中MDR/MXR转运体可能能够催化多种细胞毒性化合物的外排，在耐药性的获得中发挥关键作用。然而，尽管这些蛋白质传统上被认为是药物出口国，但MDR/MXR转运体的生理功能及其参与细胞毒性化合物耐药性的确切机制仍然存在争议。事实上，这些转运体可能输出的各种结构和功能不相关的底物多年来一直困扰着研究人员。现在的讨论已经转向至少一些MDR/MXR转运体作为细胞中自然生理作用的结果发挥其作用的可能性，而不是通过直接输出细胞毒性化合物，而MDR/MXR转运体可能在自然界中进化为其他目的而不是赋予化学保护的假设近年来得到了越来越多的支持。本文综述了模式酵母酿酒酵母中主要助酵剂超家族（MFS; drug:H+ antiporters）的药物转运体。对这些转运体的自然作用的新见解进行了描述和讨论，重点是通过后基因组研究获得或建议的知识。本文综述的新信息为这些转运蛋白的复杂作用提供了线索，包括对应激反应机制的间接调节和对膜电位和/或内部pH的控制，并特别强调了MDR/MXR-MFS转运蛋白的调节和进化的全基因组观点。
Multidrug/Multixenobiotic resistance (MDR/MXR) is a widespread phenomenon with clinical, agricultural and biotechnological implications, where MDR/MXR transporters that are presumably able to catalyze the efflux of multiple cytotoxic compounds play a key role in the acquisition of resistance. However, although these proteins have been traditionally considered drug exporters, the physiological function of MDR/MXR transporters and the exact mechanism of their involvement in resistance to cytotoxic compounds are still open to debate. In fact, the wide range of structurally and functionally unrelated substrates that these transporters are presumably able to export has puzzled researchers for years. The discussion has now shifted toward the possibility of at least some MDR/MXR transporters exerting their effect as the result of a natural physiological role in the cell, rather than through the direct export of cytotoxic compounds, while the hypothesis that MDR/MXR transporters may have evolved in nature for other purposes than conferring chemoprotection has been gaining momentum in recent years. This review focuses on the drug transporters of the Major Facilitator Superfamily (MFS; drug:H+ antiporters) in the model yeast Saccharomyces cerevisiae. New insights into the natural roles of these transporters are described and discussed, focusing on the knowledge obtained or suggested by post-genomic research. The new information reviewed here provides clues into the unexpectedly complex roles of these transporters, including a proposed indirect regulation of the stress response machinery and control of membrane potential and/or internal pH, with a special emphasis on a genome-wide view of the regulation and evolution of MDR/MXR-MFS transporters.
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影响因子：
--
作者：
Felder, T;Bogengruber, E;Briza, P
通讯作者：
Briza, P
影响因子：
4.9
作者：
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影响因子：
5
作者：
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通讯作者：
Sa-Correia, Isabel
DOI：
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发表时间：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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