Lipid bilayer stress-activated IRE-1 modulates autophagy during endoplasmic reticulum stress
Metabolic disorders such as nonalcoholic fatty liver disease (NAFLD) are emerging epidemics that affect the global population. One facet of these disorders is attributed to the disturbance of membrane lipid composition. Perturbation of endoplasmic reticulum (ER) homeostasis through alteration in mem...
| Main Authors: | , , , |
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| Format: | Journal Article |
| Language: | English |
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2018
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| Online Access: | https://hdl.handle.net/10356/89666 http://hdl.handle.net/10220/46714 |
| _version_ | 1826124308073676800 |
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| author | Koh, Jhee Hong Wang, Lei Beaudoin-Chabot, Caroline Thibault, Guillaume |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Koh, Jhee Hong Wang, Lei Beaudoin-Chabot, Caroline Thibault, Guillaume |
| author_sort | Koh, Jhee Hong |
| collection | NTU |
| description | Metabolic disorders such as nonalcoholic fatty liver disease (NAFLD) are emerging epidemics that affect the global population. One facet of these disorders is attributed to the disturbance of membrane lipid composition. Perturbation of endoplasmic reticulum (ER) homeostasis through alteration in membrane phospholipids activates the unfolded protein response (UPR) and causes dramatic transcriptional and translational changes in the cell. To restore cellular homeostasis, the three highly conserved UPR transducers ATF6, IRE1, and PERK mediate adaptive responses upon ER stress. The homeostatic UPR cascade is well characterised under conditions of proteotoxic stress, but much less so under lipid bilayer stress induced-UPR. Disrupted phosphatidylcholine (PC) synthesis in C. elegans causes lipid bilayer stress, lipid droplet accumulation and ER stress induction. Transcriptional profiling of PC-deficient worms shows a unique subset of genes regulated in a UPR-dependent manner that is independent from proteotoxic stress. Among these, we show that autophagy is modulated through the conserved IRE-1/XBP-1 axis, strongly suggesting of the importance of autophagy in maintaining cellular homeostasis during lipid bilayer induced-UPR. |
| first_indexed | 2024-10-01T06:18:31Z |
| format | Journal Article |
| id | ntu-10356/89666 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:18:31Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/896662023-02-28T17:03:28Z Lipid bilayer stress-activated IRE-1 modulates autophagy during endoplasmic reticulum stress Koh, Jhee Hong Wang, Lei Beaudoin-Chabot, Caroline Thibault, Guillaume School of Biological Sciences Endoplasmic Reticulum (ER) Unfolded Protein Response (UPR) DRNTU::Science::Biological sciences Metabolic disorders such as nonalcoholic fatty liver disease (NAFLD) are emerging epidemics that affect the global population. One facet of these disorders is attributed to the disturbance of membrane lipid composition. Perturbation of endoplasmic reticulum (ER) homeostasis through alteration in membrane phospholipids activates the unfolded protein response (UPR) and causes dramatic transcriptional and translational changes in the cell. To restore cellular homeostasis, the three highly conserved UPR transducers ATF6, IRE1, and PERK mediate adaptive responses upon ER stress. The homeostatic UPR cascade is well characterised under conditions of proteotoxic stress, but much less so under lipid bilayer stress induced-UPR. Disrupted phosphatidylcholine (PC) synthesis in C. elegans causes lipid bilayer stress, lipid droplet accumulation and ER stress induction. Transcriptional profiling of PC-deficient worms shows a unique subset of genes regulated in a UPR-dependent manner that is independent from proteotoxic stress. Among these, we show that autophagy is modulated through the conserved IRE-1/XBP-1 axis, strongly suggesting of the importance of autophagy in maintaining cellular homeostasis during lipid bilayer induced-UPR. MOE (Min. of Education, S’pore) Accepted version 2018-11-27T01:43:17Z 2019-12-06T17:30:43Z 2018-11-27T01:43:17Z 2019-12-06T17:30:43Z 2018 2018 Journal Article Koh, J. H., Wang, L., Beaudoin-Chabot, C., & Thibault, G. (2018). Lipid bilayer stress-activated IRE-1 modulates autophagy during endoplasmic reticulum stress. Journal of Cell Science, 131(22), jcs217992-. doi:10.1242/jcs.217992 0021-9533 https://hdl.handle.net/10356/89666 http://hdl.handle.net/10220/46714 10.1242/jcs.217992 208998 en Journal of Cell Science https://doi.org/10.21979/N9/OLY1FU © 2018 The Company of Biologists Ltd. This is the author created version of a work that has been peer reviewed and accepted for publication by Journal of Cell Science, The Company of Biologists Ltd. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1242/jcs.217992]. 36 p. application/pdf |
| spellingShingle | Endoplasmic Reticulum (ER) Unfolded Protein Response (UPR) DRNTU::Science::Biological sciences Koh, Jhee Hong Wang, Lei Beaudoin-Chabot, Caroline Thibault, Guillaume Lipid bilayer stress-activated IRE-1 modulates autophagy during endoplasmic reticulum stress |
| title | Lipid bilayer stress-activated IRE-1 modulates autophagy during endoplasmic reticulum stress |
| title_full | Lipid bilayer stress-activated IRE-1 modulates autophagy during endoplasmic reticulum stress |
| title_fullStr | Lipid bilayer stress-activated IRE-1 modulates autophagy during endoplasmic reticulum stress |
| title_full_unstemmed | Lipid bilayer stress-activated IRE-1 modulates autophagy during endoplasmic reticulum stress |
| title_short | Lipid bilayer stress-activated IRE-1 modulates autophagy during endoplasmic reticulum stress |
| title_sort | lipid bilayer stress activated ire 1 modulates autophagy during endoplasmic reticulum stress |
| topic | Endoplasmic Reticulum (ER) Unfolded Protein Response (UPR) DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/89666 http://hdl.handle.net/10220/46714 |
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