Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, 630-0192, Japan.
Institute of Biotechnology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet road, Cau Giay, Ha Noi, Vietnam.
Sci Rep. 2019 Sep 4;9(1):12780. doi: 10.1038/s41598-019-49146-5.
Upon dysfunction of the endoplasmic reticulum (ER), eukaryotic cells evoke the unfolded protein response (UPR), which, in yeast Saccharomyces cerevisaie cells, is promoted by the ER-located transmembrane endoribonuclease Ire1. When activated, Ire1 splices and matures the HAC1 mRNA which encodes a transcription-factor protein that is responsible for the gene induction of the UPR. Here we propose that this signaling pathway is also used in cellular adaptation upon diauxic shift, in which cells shift from fermentative phase (fast growth) to mitochondrial respiration phase (slower growth). Splicing of the HAC1 mRNA was induced upon diauxic shift of cells cultured in glucose-based media or in cells transferred from glucose-based medium to non-fermentable glycerol-based medium. Activation of Ire1 in this situation was not due to ER accumulation of unfolded proteins, and was mediated by reactive oxygen species (ROS), which are byproducts of aerobic respiration. Here we also show that the UPR induced by diauxic shift causes enlargement of the mitochondria, and thus contributes to cellular growth under non-fermentative conditions, in addition to transcriptional induction of the canonical UPR target genes, which includes those encoding ER-located molecular chaperones and protein-folding enzymes.
当内质网（ER）功能失调时，真核细胞会引发未折叠蛋白反应（UPR），在酵母酿酒酵母细胞中，该反应由位于 ER 中的跨膜内切核糖核酸酶 Ire1 促进。当被激活时，Ire1 剪接并成熟 HAC1 mRNA，该 mRNA 编码一种转录因子蛋白，负责 UPR 的基因诱导。在这里，我们提出，该信号通路也用于细胞在双相转换时的适应，其中细胞从发酵阶段（快速生长）转换到线粒体呼吸阶段（生长较慢）。当在基于葡萄糖的培养基中培养的细胞或从基于葡萄糖的培养基转移到不可发酵的甘油基培养基中的细胞发生双相转换时，HAC1 mRNA 的剪接被诱导。在这种情况下，Ire1 的激活不是由于未折叠蛋白在 ER 中的积累，而是由活性氧（ROS）介导的，ROS 是有氧呼吸的副产物。在这里，我们还表明，双相转换诱导的 UPR 导致线粒体增大，从而有助于非发酵条件下的细胞生长，除了经典 UPR 靶基因的转录诱导外，这些基因包括那些编码 ER 定位分子伴侣和蛋白折叠酶的基因。
