Citation | Kim HE, Grant AR, Simic MS, Kohnz RA, Nomura DK, Durieux J, Riera CE, Sanchez M, Kapernick E, Wolff S, Dillin A. Lipid Biosynthesis Coordinates a Mitochondrial-to-Cytosolic Stress Response. Cell, 2016. |
PubMed ID | 27610574 |
Short Description | Lipid Biosynthesis Coordinates a Mitochondrial-to-Cytosolic Stress Response. GEO Record: GSE83722 Platform: GPL200 Download gene-centric, log2 transformed data: WBPaper00050407.ce.mr.csv |
# of Conditions | 12 |
Full Description
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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 ER, 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. Experimental Details: WBPaper00050407:control(RNAi)_rep1 WBPaper00050407:control(RNAi)_rep2 WBPaper00050407:control(RNAi)_rep3 WBPaper00050407:hsp-6(RNAi)_rep1 WBPaper00050407:hsp-6(RNAi)_rep2 WBPaper00050407:hsp-6(RNAi)_rep3 WBPaper00050407:hsp-6(RNAi);hsf-1(RNAi)_rep1 WBPaper00050407:hsp-6(RNAi);hsf-1(RNAi)_rep2 WBPaper00050407:hsp-6(RNAi);hsf-1(RNAi)_rep3 WBPaper00050407:hsp-6(RNAi);dve-1(RNAi)_rep1 WBPaper00050407:hsp-6(RNAi);dve-1(RNAi)_rep2 WBPaper00050407:hsp-6(RNAi);dve-1(RNAi)_rep3. |
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