Dissociation of ERMES clusters plays a key role in attenuating the endoplasmic reticulum stress
Yuriko Kakimoto-Takeda,
Rieko Kojima,
Hiroya Shiino,
Manatsu Shinmyo,
Kazuo Kurokawa,
Akihiko Nakano,
Toshiya Endo,
Yasushi Tamura
Affiliations
Yuriko Kakimoto-Takeda
Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan
Rieko Kojima
Faculty of Science, Yamagata University, 1-4-12 Kojirakawa-machi, Yamagata 990-8560, Japan
Hiroya Shiino
Faculty of Science, Yamagata University, 1-4-12 Kojirakawa-machi, Yamagata 990-8560, Japan
Manatsu Shinmyo
Faculty of Science, Yamagata University, 1-4-12 Kojirakawa-machi, Yamagata 990-8560, Japan
Kazuo Kurokawa
Live Cell Super-Resolution Imaging Research Team, RIKEN Center for Advanced Photonics, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
Akihiko Nakano
Live Cell Super-Resolution Imaging Research Team, RIKEN Center for Advanced Photonics, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
Toshiya Endo
Faculty 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, Japan
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.
