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000141390 1001_ $$0P:(DE-HGF)0$$aRunkel, Eva D$$b0
000141390 245__ $$aSurveillance-activated defenses block the ROS-induced mitochondrial unfolded protein response.
000141390 260__ $$aSan Francisco, Calif.$$bPublic Library of Science$$c2013
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000141390 520__ $$aDisturbance of cellular functions results in the activation of stress-signaling pathways that aim at restoring homeostasis. We performed a genome-wide screen to identify components of the signal transduction of the mitochondrial unfolded protein response (UPR(mt)) to a nuclear chaperone promoter. We used the ROS generating complex I inhibitor paraquat to induce the UPR(mt), and we employed RNAi exposure post-embryonically to allow testing genes whose knockdown results in embryonic lethality. We identified 54 novel regulators of the ROS-induced UPR(mt). Activation of the UPR(mt), but not of other stress-signaling pathways, failed when homeostasis of basic cellular mechanisms such as translation and protein transport were impaired. These mechanisms are monitored by a recently discovered surveillance system that interprets interruption of these processes as pathogen attack and depends on signaling through the JNK-like MAP-kinase KGB-1. Mutation of kgb-1 abrogated the inhibition of ROS-induced UPR(mt), suggesting that surveillance-activated defenses specifically inhibit the UPR(mt) but do not compromise activation of the heat shock response, the UPR of the endoplasmic reticulum, or the SKN-1/Nrf2 mediated response to cytosolic stress. In addition, we identified PIFK-1, the orthologue of the Drosophila PI 4-kinase four wheel drive (FWD), and found that it is the only known factor so far that is essential for the unfolded protein responses of both mitochondria and endoplasmic reticulum. This suggests that both UPRs may share a common membrane associated mechanism.
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000141390 650_7 $$2NLM Chemicals$$aATFS-1 protein, C elegans
000141390 650_7 $$2NLM Chemicals$$aATP-Binding Cassette Transporters
000141390 650_7 $$2NLM Chemicals$$aCaenorhabditis elegans Proteins
000141390 650_7 $$2NLM Chemicals$$aHAF-1 protein, C elegans
000141390 650_7 $$2NLM Chemicals$$aMolecular Chaperones
000141390 650_7 $$2NLM Chemicals$$aReactive Oxygen Species
000141390 650_7 $$2NLM Chemicals$$aTranscription Factors
000141390 650_7 $$0EC 2.7.11.24$$2NLM Chemicals$$aJNK Mitogen-Activated Protein Kinases
000141390 650_7 $$0EC 2.7.11.24$$2NLM Chemicals$$aKGB-1 protein, C elegans
000141390 650_7 $$0PLG39H7695$$2NLM Chemicals$$aParaquat
000141390 650_2 $$2MeSH$$aATP-Binding Cassette Transporters: metabolism
000141390 650_2 $$2MeSH$$aAnimals
000141390 650_2 $$2MeSH$$aCaenorhabditis elegans: genetics
000141390 650_2 $$2MeSH$$aCaenorhabditis elegans: growth & development
000141390 650_2 $$2MeSH$$aCaenorhabditis elegans: metabolism
000141390 650_2 $$2MeSH$$aCaenorhabditis elegans Proteins: genetics
000141390 650_2 $$2MeSH$$aCaenorhabditis elegans Proteins: metabolism
000141390 650_2 $$2MeSH$$aCell Nucleus: genetics
000141390 650_2 $$2MeSH$$aCell Nucleus: metabolism
000141390 650_2 $$2MeSH$$aEndoplasmic Reticulum: genetics
000141390 650_2 $$2MeSH$$aEndoplasmic Reticulum: metabolism
000141390 650_2 $$2MeSH$$aJNK Mitogen-Activated Protein Kinases: genetics
000141390 650_2 $$2MeSH$$aJNK Mitogen-Activated Protein Kinases: metabolism
000141390 650_2 $$2MeSH$$aMitochondria: drug effects
000141390 650_2 $$2MeSH$$aMitochondria: metabolism
000141390 650_2 $$2MeSH$$aMolecular Chaperones
000141390 650_2 $$2MeSH$$aParaquat: pharmacology
000141390 650_2 $$2MeSH$$aPhosphorylation
000141390 650_2 $$2MeSH$$aProtein Folding
000141390 650_2 $$2MeSH$$aReactive Oxygen Species: metabolism
000141390 650_2 $$2MeSH$$aReactive Oxygen Species: toxicity
000141390 650_2 $$2MeSH$$aSignal Transduction: drug effects
000141390 650_2 $$2MeSH$$aTranscription Factors: metabolism
000141390 650_2 $$2MeSH$$aUnfolded Protein Response: drug effects
000141390 7001_ $$0P:(DE-2719)2810461$$aLiu, Shu$$b1$$udzne
000141390 7001_ $$0P:(DE-HGF)0$$aBaumeister, Ralf$$b2$$eCorresponding author
000141390 7001_ $$0P:(DE-HGF)0$$aSchulze, Ekkehard$$b3
000141390 77318 $$2Crossref$$3journal-article$$a10.1371/journal.pgen.1003346$$b : Public Library of Science (PLoS), 2013-03-14$$n3$$pe1003346$$tPLoS Genetics$$v9$$x1553-7404$$y2013
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000141390 8564_ $$uhttps://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1003346
000141390 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597513
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