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| Status |
Public on Sep 25, 2012 |
| Title |
The Membrane Stress Response Buffers Lethal Effects of Lipid Disequilibrium by Reprogramming the Protein Homeostasis Network |
| Organism |
Saccharomyces cerevisiae |
| Experiment type |
Expression profiling by array
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| Summary |
Lipid composition can differ widely among organelles and even between leaflets of a membrane. Lipid homeostasis is critical because disequilibrium can have disease outcomes. Despite their importance, mechanisms maintaining lipid homeostasis remain poorly understood. Here, we establish a model system to study the global effects of lipid imbalance. Quantitative lipid profiling was integral to monitor changes to lipid composition and for system validation. Applying global transcriptional and proteomic analyses, a dramatically altered biochemical landscape was revealed from adaptive cells. The resulting composite regulation we term the ?membrane stress response? (MSR) confers compensation, not through restoration of lipid composition, but by remodeling the protein homeostasis network. To validate its physiological significance, we analyzed the unfolded protein response (UPR), one facet of the MSR and a key regulator of protein homeostasis. We demonstrate that the UPR maintains protein biogenesis, quality control, and membrane integrity?functions otherwise lethally compromised in lipid dysregulated cells.
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| Overall design |
Genes expression from early log phase of CHO2, OPI3, and PAH1 knockout cell and untreated and DTT-treated WT cells. RNA was prepared from independent triplicate samples.
Array sets performed and collected on different dates are as follows:
Array 1, Day 1:
WT_rep1
pah1_rep1
cho2_rep1
opi3_rep1
Array 2, Day 2:
WT_rep2
WT_rep3
WT_Tm_rep1
WT_DTT_rep1
Array 3, Day 2:
WT_DTT_rep2
WT_DTT_rep3
cho2_rep2
cho2_rep3
Array 4, Day 2:
pah1_rep2
pah1_rep3
opi3_rep2
opi3_rep3
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| Contributor(s) |
Thibault G, Ng DT |
| Citation(s) |
23000174 |
| |
| Submission date |
Jul 17, 2012 |
| Last update date |
Sep 25, 2012 |
| Contact name |
Guillaume Thibault |
| E-mail(s) |
guillou1976@gmail.com
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| Organization name |
Temasek Life Sciences Laboratory
|
| Department |
Cell Stress and Homeostasis
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| Lab |
Davis Ng
|
| Street address |
1 Research Link, National University of Singapore
|
| City |
Singapore |
| ZIP/Postal code |
117604 |
| Country |
Singapore |
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| Platforms (1) |
| GPL9294 |
Agilent-015072 Yeast Oligo Microarray 4x44K G2519F (Probe Name version) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA170841 |
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