Nishida Nao, Jing Dongyu, Kuroda Kouichi, Ueda Mitsuyoshi
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.
Curr Genet. 2014 Aug;60(3):149-62. doi: 10.1007/s00294-013-0419-5. Epub 2013 Dec 31.
Organic solvents are toxic to living cells. In eukaryotes, cells with organic solvent tolerance have only been found in Saccharomyces cerevisiae. Although several factors contributing to organic solvent tolerance have been identified in previous studies, the mechanism of how yeast cells naturally respond to organic solvent stress is not known. We demonstrated that the pleiotropic drug resistance (PDR) pathway contributed to response to organic solvent stress. Activation of the PDR pathway by mutations in the transcription factors Pdr1p and Pdr3p led to organic solvent tolerance. Exposure to organic solvents also induced transcription levels of PDR5, which encodes a major drug efflux pump. Overproduction of Pdr5p improved organic solvent tolerance, presumably by exporting organic solvents out of the cell. In addition, we showed that the cell wall integrity (CWI) pathway was induced in response to organic solvents to upregulate genes encoding the cell wall-related proteins Wsc3p and Ynl190wp. WSC3 and YNL190W were upregulated independently of the PDR pathway. Among the components of the CWI pathway, the cell surface sensors (Wsc3p and Mid2p) and the transcription factors (Swi4p and Swi6p) appeared to be particularly involved in the response to organic solvents. Our findings indicate that S. cerevisiae activates two different signaling pathways, the PDR pathway and the CWI pathway, to cope with stresses from organic solvents.
有机溶剂对活细胞有毒性。在真核生物中，仅在酿酒酵母中发现了具有有机溶剂耐受性的细胞。尽管先前的研究已经确定了几个有助于有机溶剂耐受性的因素，但酵母细胞如何自然应对有机溶剂胁迫的机制尚不清楚。我们证明了多药耐药（PDR）途径有助于应对有机溶剂胁迫。转录因子Pdr1p和Pdr3p的突变激活PDR途径会导致有机溶剂耐受性。暴露于有机溶剂也会诱导编码主要药物外排泵的PDR5的转录水平。过量表达Pdr5p可提高有机溶剂耐受性，可能是通过将有机溶剂输出细胞外实现的。此外，我们表明细胞壁完整性（CWI）途径会因有机溶剂而被诱导，从而上调编码细胞壁相关蛋白Wsc3p和Ynl190p的基因。WSC3和YNL190W的上调独立于PDR途径。在CWI途径的组成部分中，细胞表面传感器（Wsc3p和Mid2p）和转录因子（Swi4p和Swi6p）似乎特别参与了对有机溶剂的响应。我们的研究结果表明，酿酒酵母激活了两种不同的信号通路，即PDR途径和CWI途径，以应对来自有机溶剂的胁迫。
