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| Status |
Public on Sep 08, 2016 |
| Title |
Lipid biosynthesis coordinates a Mitochondrial to Cytosolic Stress Response |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Expression profiling by array
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| Summary |
Defects in mitochondrial metabolism have been increasingly linked with age-onset protein misfolding diseases such as Alzheimer’s, Parkinson’s, and Huntington’s. In response to protein folding stress, compartment-specific unfolded protein responses (UPRs) within the endoplasmic reticulum, mitochondria, and cytosol work in parallel to ensure cellular protein homeostasis. While perturbation of individual compartments can make other compartments more susceptible to protein stress, the cellular conditions that trigger cross-communication between the individual UPRs remain poorly understood.
We have uncovered a conserved, robust mechanism linking mitochondrial protein homeostasis and the cytosolic folding environment through changes in lipid homeostasis. Metabolic restructuring caused by mitochondrial stress or small molecule activators trigger changes in gene expression coordinated uniquely by both the mitochondrial and cytosolic UPRs, protecting the cell from disease-associated proteins. Our data suggest an intricate and unique system of communication between UPRs in response to metabolic changes that could unveil new targets for diseases of protein misfolding.
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| Overall design |
Because the induction of the MCSR due to hsp-6 RNAi required both hsf-1 and dve-1, key transcription factors required for the HSR and UPRmt, respectively, we asked which gene sets are coordinately regulated by both factors. We performed microarray analyses to determine which genes have their expression altered by hsp-6 RNAi and whether these genes are regulated either by hsf-1, dve-1 or both
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| Contributor(s) |
Kim H, Grant AR, Simic MS, Kohnz RA, Nomura DK, Durieux J, Riera CE, Sanchez M, Kapernick E, Wolff S, Dillin A |
| Citation(s) |
27610574 |
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| Submission date |
Jun 26, 2016 |
| Last update date |
Dec 08, 2016 |
| Contact name |
Ana Rodrigues Grant |
| E-mail(s) |
anapcr@umich.edu
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| Organization name |
University of Michigan
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| Department |
Computational Medicine & Bioinformatics
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| Street address |
100 Washtenaw Avenue
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| City |
Ann Arbor |
| State/province |
MI |
| ZIP/Postal code |
48109 |
| Country |
USA |
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| Platforms (1) |
| GPL200 |
[Celegans] Affymetrix C. elegans Genome Array |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA326871 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE83722_RAW.tar |
25.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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