The yeast FIT2 homologs are necessary to maintain cellular proteostasis and membrane lipid homeostasis
Lipid droplets (LDs) are implicated in conditions of lipid and protein dysregulation. The fat storage-inducing transmembrane (FIT; also known as FITM) family induces LD formation. Here, we establish a model system to study the role of the Saccharomyces cerevisiae FIT homologues (ScFIT), SCS3 and YFT...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2022
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| Online Access: | https://hdl.handle.net/10356/161980 |
| _version_ | 1824455136746930176 |
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| author | Yap, Wei Sheng Shyu Jr., Peter Gaspar, Maria Laura Jesch, Stephen A. Marvalim, Charlie Prinz, William A. Henry, Susan A. Thibault, Guillaume |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Yap, Wei Sheng Shyu Jr., Peter Gaspar, Maria Laura Jesch, Stephen A. Marvalim, Charlie Prinz, William A. Henry, Susan A. Thibault, Guillaume |
| author_sort | Yap, Wei Sheng |
| collection | NTU |
| description | Lipid droplets (LDs) are implicated in conditions of lipid and protein dysregulation. The fat storage-inducing transmembrane (FIT; also known as FITM) family induces LD formation. Here, we establish a model system to study the role of the Saccharomyces cerevisiae FIT homologues (ScFIT), SCS3 and YFT2, in the proteostasis and stress response pathways. While LD biogenesis and basal endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) remain unaltered in ScFIT mutants, SCS3 was found to be essential for proper stress-induced UPR activation and for viability in the absence of the sole yeast UPR transducer IRE1 Owing to not having a functional UPR, cells with mutated SCS3 exhibited an accumulation of triacylglycerol within the ER along with aberrant LD morphology, suggesting that there is a UPR-dependent compensatory mechanism that acts to mitigate lack of SCS3 Additionally, SCS3 was necessary to maintain phospholipid homeostasis. Strikingly, global protein ubiquitylation and the turnover of both ER and cytoplasmic misfolded proteins is impaired in ScFITΔ cells, while a screen for interacting partners of Scs3 identifies components of the proteostatic machinery as putative targets. Together, our data support a model where ScFITs play an important role in lipid metabolism and proteostasis beyond their defined roles in LD biogenesis.This article has an associated First Person interview with the first author of the paper. |
| first_indexed | 2025-02-19T03:33:25Z |
| format | Journal Article |
| id | ntu-10356/161980 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:33:25Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | ntu-10356/1619802023-02-28T17:11:16Z The yeast FIT2 homologs are necessary to maintain cellular proteostasis and membrane lipid homeostasis Yap, Wei Sheng Shyu Jr., Peter Gaspar, Maria Laura Jesch, Stephen A. Marvalim, Charlie Prinz, William A. Henry, Susan A. Thibault, Guillaume School of Biological Sciences Institute of Molecular and Cell Biology, A*STAR Science::Medicine Endoplasmic Reticulum-Associated Degradation Lipid Droplet Proteostasis Phospholipid Metabolism Unfolded Protein Response Lipid droplets (LDs) are implicated in conditions of lipid and protein dysregulation. The fat storage-inducing transmembrane (FIT; also known as FITM) family induces LD formation. Here, we establish a model system to study the role of the Saccharomyces cerevisiae FIT homologues (ScFIT), SCS3 and YFT2, in the proteostasis and stress response pathways. While LD biogenesis and basal endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) remain unaltered in ScFIT mutants, SCS3 was found to be essential for proper stress-induced UPR activation and for viability in the absence of the sole yeast UPR transducer IRE1 Owing to not having a functional UPR, cells with mutated SCS3 exhibited an accumulation of triacylglycerol within the ER along with aberrant LD morphology, suggesting that there is a UPR-dependent compensatory mechanism that acts to mitigate lack of SCS3 Additionally, SCS3 was necessary to maintain phospholipid homeostasis. Strikingly, global protein ubiquitylation and the turnover of both ER and cytoplasmic misfolded proteins is impaired in ScFITΔ cells, while a screen for interacting partners of Scs3 identifies components of the proteostatic machinery as putative targets. Together, our data support a model where ScFITs play an important role in lipid metabolism and proteostasis beyond their defined roles in LD biogenesis.This article has an associated First Person interview with the first author of the paper. Nanyang Technological University National Research Foundation (NRF) Published version This work was supported by the Nanyang Assistant Professorship programme from the Nanyang Technological University to G.T., the National Research Foundation, Singapore, under its NRF-NSFC joint research grant call (Synthetic Biology, NRF2018NRFNSFC003SB-006) to G.T., the Nanyang Technological University Research Scholarship to P.J.S. (predoctoral fellowship), the National Institutes of Health (NIH) grant GM-19629 to S.A.H., the Intramural Research Program of the NIH to W.A.P., The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to W.A.P. 2022-09-30T02:19:18Z 2022-09-30T02:19:18Z 2020 Journal Article Yap, W. S., Shyu Jr., P., Gaspar, M. L., Jesch, S. A., Marvalim, C., Prinz, W. A., Henry, S. A. & Thibault, G. (2020). The yeast FIT2 homologs are necessary to maintain cellular proteostasis and membrane lipid homeostasis. Journal of Cell Science, 133(21), jcs248526-. https://dx.doi.org/10.1242/jcs.248526 0021-9533 https://hdl.handle.net/10356/161980 10.1242/jcs.248526 33033181 2-s2.0-85095861718 21 133 jcs248526 en NRF2018NRFNSFC003SB-006 Journal of Cell Science 10.21979/N9/I7MXVP © 2020 The Author(s). All rights reserved. This paper was published by The Company of Biologists Ltd in Journal of Cell Science and is made available with permission of The Author(s). application/pdf |
| spellingShingle | Science::Medicine Endoplasmic Reticulum-Associated Degradation Lipid Droplet Proteostasis Phospholipid Metabolism Unfolded Protein Response Yap, Wei Sheng Shyu Jr., Peter Gaspar, Maria Laura Jesch, Stephen A. Marvalim, Charlie Prinz, William A. Henry, Susan A. Thibault, Guillaume The yeast FIT2 homologs are necessary to maintain cellular proteostasis and membrane lipid homeostasis |
| title | The yeast FIT2 homologs are necessary to maintain cellular proteostasis and membrane lipid homeostasis |
| title_full | The yeast FIT2 homologs are necessary to maintain cellular proteostasis and membrane lipid homeostasis |
| title_fullStr | The yeast FIT2 homologs are necessary to maintain cellular proteostasis and membrane lipid homeostasis |
| title_full_unstemmed | The yeast FIT2 homologs are necessary to maintain cellular proteostasis and membrane lipid homeostasis |
| title_short | The yeast FIT2 homologs are necessary to maintain cellular proteostasis and membrane lipid homeostasis |
| title_sort | yeast fit2 homologs are necessary to maintain cellular proteostasis and membrane lipid homeostasis |
| topic | Science::Medicine Endoplasmic Reticulum-Associated Degradation Lipid Droplet Proteostasis Phospholipid Metabolism Unfolded Protein Response |
| url | https://hdl.handle.net/10356/161980 |
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