Dissociation of ERMES clusters plays a key role in attenuating the endoplasmic reticulum stress

Summary: In 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...

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Main Authors: Yuriko Kakimoto-Takeda, Rieko Kojima, Hiroya Shiino, Manatsu Shinmyo, Kazuo Kurokawa, Akihiko Nakano, Toshiya Endo, Yasushi Tamura
Format: Article
Language:English
Published: Elsevier 2022-11-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004222016340
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author Yuriko Kakimoto-Takeda
Rieko Kojima
Hiroya Shiino
Manatsu Shinmyo
Kazuo Kurokawa
Akihiko Nakano
Toshiya Endo
Yasushi Tamura
author_facet Yuriko Kakimoto-Takeda
Rieko Kojima
Hiroya Shiino
Manatsu Shinmyo
Kazuo Kurokawa
Akihiko Nakano
Toshiya Endo
Yasushi Tamura
author_sort Yuriko Kakimoto-Takeda
collection DOAJ
description Summary: In 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.
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spelling doaj.art-e1aba48a5485490da62f70182a6e4bc22022-12-22T03:27:33ZengElsevieriScience2589-00422022-11-012511105362Dissociation of ERMES clusters plays a key role in attenuating the endoplasmic reticulum stressYuriko Kakimoto-Takeda0Rieko Kojima1Hiroya Shiino2Manatsu Shinmyo3Kazuo Kurokawa4Akihiko Nakano5Toshiya Endo6Yasushi Tamura7Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, JapanFaculty of Science, Yamagata University, 1-4-12 Kojirakawa-machi, Yamagata 990-8560, JapanFaculty of Science, Yamagata University, 1-4-12 Kojirakawa-machi, Yamagata 990-8560, JapanFaculty of Science, Yamagata University, 1-4-12 Kojirakawa-machi, Yamagata 990-8560, JapanLive Cell Super-Resolution Imaging Research Team, RIKEN Center for Advanced Photonics, 2-1 Hirosawa, Wako, Saitama 351-0198, JapanLive Cell Super-Resolution Imaging Research Team, RIKEN Center for Advanced Photonics, 2-1 Hirosawa, Wako, Saitama 351-0198, JapanFaculty of Life Sciences, Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku, Kyoto 603-8555, Japan; Institute for Protein Dynamics, Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku, Kyoto 603-8555, JapanFaculty of Science, Yamagata University, 1-4-12 Kojirakawa-machi, Yamagata 990-8560, Japan; Corresponding authorSummary: In 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.http://www.sciencedirect.com/science/article/pii/S2589004222016340Biological sciencesCell biologyFunctional aspects of cell biology
spellingShingle Yuriko Kakimoto-Takeda
Rieko Kojima
Hiroya Shiino
Manatsu Shinmyo
Kazuo Kurokawa
Akihiko Nakano
Toshiya Endo
Yasushi Tamura
Dissociation of ERMES clusters plays a key role in attenuating the endoplasmic reticulum stress
iScience
Biological sciences
Cell biology
Functional aspects of cell biology
title Dissociation of ERMES clusters plays a key role in attenuating the endoplasmic reticulum stress
title_full Dissociation of ERMES clusters plays a key role in attenuating the endoplasmic reticulum stress
title_fullStr Dissociation of ERMES clusters plays a key role in attenuating the endoplasmic reticulum stress
title_full_unstemmed Dissociation of ERMES clusters plays a key role in attenuating the endoplasmic reticulum stress
title_short Dissociation of ERMES clusters plays a key role in attenuating the endoplasmic reticulum stress
title_sort dissociation of ermes clusters plays a key role in attenuating the endoplasmic reticulum stress
topic Biological sciences
Cell biology
Functional aspects of cell biology
url http://www.sciencedirect.com/science/article/pii/S2589004222016340
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