文章基本信息

标题：Dissociation of ERMES clusters plays a key role in attenuating the endoplasmic reticulum stress
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作者：Yuriko Kakimoto-Takeda ; Rieko Kojima ; Hiroya Shiino 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：11
页码：1-26
DOI：10.1016/j.isci.2022.105362
语种：English
出版社：Elsevier
摘要：SummaryIn yeast, ERMES, which mediates phospholipid transport between the ER and mitochondria, forms a limited number of oligomeric clusters at ER-mitochondria contact sites in a cell. Although the number of the ERMES clusters appears to be regulated to maintain proper inter-organelle phospholipid trafficking, its underlying mechanism and physiological relevance remain poorly understood. Here, we show that mitochondrial dynamics control the number of ERMES clusters. Moreover, we find that ER stress causes dissociation of the ERMES clusters independently of Ire1 and Hac1, canonical ER-stress response pathway components, leading to a delay in the phospholipid transport from the ER to mitochondria. Our biochemical and genetic analyses strongly suggest that the impaired phospholipid transport contributes to phospholipid accumulation in the ER, expanding the ER for ER stress attenuation. We thus propose that the ERMES dissociation constitutes an overlooked pathway of the ER stress response that operates in addition to the canonical Ire1/Hac1-dependent pathway.Graphical abstractDisplay OmittedHighlights•Mitochondrial fusion and division regulate the clustering of the ERMES complex•ER stress leads to dissociation of the ERMES clusters independently of Ire1 and Hac1•The dissociated ERMES complexes have less activity in transporting phospholipids•The defective phospholipid transport may cause the ER expansion to relieve ER stressBiological sciences; Cell biology; Functional aspects of cell biology.