VMP1 affects endoplasmic reticulum stress sensitivity via differential modulation of the three unfolded protein response arms
Summary: Consisting of three signaling pathways, the unfolded protein response (UPR) can be either protective or detrimental to cells that undergo ER stress. Elaborate regulation of the UPR is key to the cell-fate decision, but how it is achieved remains vague. Here, by studying cells deficient in v...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723002206 |
| _version_ | 1811159990342254592 |
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| author | Tao Li Hongyu Zhao Gaofeng Guo Shuwei Xia Likun Wang |
| author_facet | Tao Li Hongyu Zhao Gaofeng Guo Shuwei Xia Likun Wang |
| author_sort | Tao Li |
| collection | DOAJ |
| description | Summary: Consisting of three signaling pathways, the unfolded protein response (UPR) can be either protective or detrimental to cells that undergo ER stress. Elaborate regulation of the UPR is key to the cell-fate decision, but how it is achieved remains vague. Here, by studying cells deficient in vacuole membrane protein 1 (VMP1), a UPR regulator, we report a model of UPR regulation in which the three pathways are divergently controlled. Under basal conditions, calcium binding specifically activates PERK. Under ER stress, ER-mitochondria interaction-induced mitochondrial stress cooperates with PERK to suppress IRE1α and ATF6 by decelerating global protein synthesis. Such sophisticated regulation commits limited activation of the UPR yet refrains from UPR hyperactivation, protecting cells from chronic ER stress despite decreasing cell proliferation. Therefore, our study reveals interorganelle-interaction-dependent and calcium-dependent regulation of the UPR that dictates cell fate. |
| first_indexed | 2024-04-10T05:50:06Z |
| format | Article |
| id | doaj.art-d20575ce9a3c4d099f1126d673686965 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-10T05:50:06Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-d20575ce9a3c4d099f1126d6736869652023-03-05T04:24:20ZengElsevierCell Reports2211-12472023-03-01423112209VMP1 affects endoplasmic reticulum stress sensitivity via differential modulation of the three unfolded protein response armsTao Li0Hongyu Zhao1Gaofeng Guo2Shuwei Xia3Likun Wang4National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, P.R. ChinaNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. ChinaNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, P.R. ChinaNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, P.R. ChinaNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, P.R. China; Corresponding authorSummary: Consisting of three signaling pathways, the unfolded protein response (UPR) can be either protective or detrimental to cells that undergo ER stress. Elaborate regulation of the UPR is key to the cell-fate decision, but how it is achieved remains vague. Here, by studying cells deficient in vacuole membrane protein 1 (VMP1), a UPR regulator, we report a model of UPR regulation in which the three pathways are divergently controlled. Under basal conditions, calcium binding specifically activates PERK. Under ER stress, ER-mitochondria interaction-induced mitochondrial stress cooperates with PERK to suppress IRE1α and ATF6 by decelerating global protein synthesis. Such sophisticated regulation commits limited activation of the UPR yet refrains from UPR hyperactivation, protecting cells from chronic ER stress despite decreasing cell proliferation. Therefore, our study reveals interorganelle-interaction-dependent and calcium-dependent regulation of the UPR that dictates cell fate.http://www.sciencedirect.com/science/article/pii/S2211124723002206CP: Cell biology |
| spellingShingle | Tao Li Hongyu Zhao Gaofeng Guo Shuwei Xia Likun Wang VMP1 affects endoplasmic reticulum stress sensitivity via differential modulation of the three unfolded protein response arms Cell Reports CP: Cell biology |
| title | VMP1 affects endoplasmic reticulum stress sensitivity via differential modulation of the three unfolded protein response arms |
| title_full | VMP1 affects endoplasmic reticulum stress sensitivity via differential modulation of the three unfolded protein response arms |
| title_fullStr | VMP1 affects endoplasmic reticulum stress sensitivity via differential modulation of the three unfolded protein response arms |
| title_full_unstemmed | VMP1 affects endoplasmic reticulum stress sensitivity via differential modulation of the three unfolded protein response arms |
| title_short | VMP1 affects endoplasmic reticulum stress sensitivity via differential modulation of the three unfolded protein response arms |
| title_sort | vmp1 affects endoplasmic reticulum stress sensitivity via differential modulation of the three unfolded protein response arms |
| topic | CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723002206 |
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