A non-canonical unfolded protein response pathway and mitochondrial dynamics control the number of ER-mitochondria contact sites
A non-canonical unfolded protein response pathway and mitochondrial dynamics control the number of ER-mitochondria contact sites
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DOI：
10.1101/684753
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发表时间：
2019-06
期刊：
影响因子：
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通讯作者：
R. Kojima;Yuriko Kakimoto;Manatsu Shinmyo;Kazuo Kurokawa;A. Nakano;T. Endo;Y. Tamura
中科院分区：
文献类型：
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作者：
R. Kojima;Yuriko Kakimoto;Manatsu Shinmyo;Kazuo Kurokawa;A. Nakano;T. Endo;Y. Tamura
线粒体通过其融合与分裂之间的最佳平衡来维持其形态和功能。在这里，我们报告了一个新的作用，线粒体动力学在控制的ER-线粒体遇到结构（ERMES）集群在酵母细胞中的数量。线粒体融合或分裂的丧失分别导致细胞中观察到的ERMES病灶数量增加或减少。因此，ERMES复合物似乎彼此聚簇，并且线粒体分裂可以抑制不期望的ERMES超聚簇。此外，我们的显微镜分析表明，ER应力诱导ERMES集群的解离，增加ERMES病灶的数量，即使在没有Ire 1和Hac 1，这是UPR反应的重要因素。有趣的是，我们发现ER应激以ERMES功能依赖的方式导致ER和线粒体膜的扩张。这些发现意味着细胞配备了两个独立的调节机制，控制ER-线粒体接触位点的数量，以满足细胞和环境的需求。
Mitochondria maintain their morphology and functions through the optimized balance between the mitochondrial fusion and division. Here we report a novel role of mitochondrial dynamics in controlling the number of ER-mitochondria encounter structure (ERMES) clusters in a yeast cell. Loss of mitochondrial fusion or division caused the increased or decreased number, respectively, of ERMES foci observed in cells. ERMES complexes, therefore, appear to cluster with each other and mitochondrial division may inhibit undesired ERMES hyper-clustering. Furthermore, our microscopic analyses suggest that ER stress induces dissociation of ERMES clusters, increasing the number of ERMES foci even in the absence of Ire1 and Hac1, which are essential factors for the UPR response. Interestingly, we found that ER stress leads to expansion of both the ER and mitochondrial membranes in an ERMES function-dependent manner. These findings imply that a cell is equipped with two independent regulatory mechanisms controlling the number of ER-mitochondria contact sites to meet the cellular as well as environmental demands.