Nishida-Aoki Nao, Mori Hitoshi, Kuroda Kouichi, Ueda Mitsuyoshi
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.
Curr Genet. 2015 May;61(2):153-64. doi: 10.1007/s00294-014-0463-9. Epub 2014 Dec 7.
In Saccharomyces cerevisiae, we have demonstrated that organic solvent stress activated the pleiotropic drug resistance (PDR) pathway, which involves the transcription factors Pdr1p and Pdr3p. Pdr1p and Pdr3p are functionally homologous in multidrug resistance, although Pdr3p has been reported to have some distinct functions. Here, we analyzed the functions of Pdr1p and Pdr3p during the cellular response to isooctane, as a representative of organic solvents, and observed the differential functions of Pdr1p and Pdr3p. In response to organic solvent stress, only Pdr3p contributed to the regulation of downstream genes of the PDR pathway, while Pdr1p had a rather inhibitory role on transcriptional induction through competition with Pdr3p for binding to their recognition sequence, pleiotropic drug response element. Our results demonstrated that organic solvent stress was likely to damage mitochondria, causing generation of reactive oxygen species and mitochondrial fragmentation, and to activate retrograde signaling pathway via Pdr3p to upregulate PDR5 expression. Therefore, the unique function of Pdr3p in organic solvent stress distinguishes this pathway from the multidrug response.
在酿酒酵母中，我们已经证明有机溶剂胁迫会激活多药耐药性（PDR）途径，该途径涉及转录因子Pdr1p和Pdr3p。Pdr1p和Pdr3p在多药耐药性方面功能同源，尽管据报道Pdr3p具有一些独特的功能。在这里，我们分析了Pdr1p和Pdr3p在细胞对作为有机溶剂代表的异辛烷的反应过程中的功能，并观察到了Pdr1p和Pdr3p的不同功能。在有机溶剂胁迫下，只有Pdr3p参与PDR途径下游基因的调控，而Pdr1p通过与Pdr3p竞争结合其识别序列（多药反应元件）对转录诱导具有相当的抑制作用。我们的结果表明，有机溶剂胁迫可能会损害线粒体，导致活性氧的产生和线粒体碎片化，并通过Pdr3p激活逆行信号通路以上调PDR5的表达。因此，Pdr3p在有机溶剂胁迫中的独特功能使该途径与多药反应有所区别。
