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@ARTICLE{Runkel:141390,
author = {Runkel, Eva D and Liu, Shu and Baumeister, Ralf and
Schulze, Ekkehard},
title = {{S}urveillance-activated defenses block the {ROS}-induced
mitochondrial unfolded protein response.},
journal = {PLoS Genetics},
volume = {9},
number = {3},
issn = {1553-7404},
address = {San Francisco, Calif.},
publisher = {Public Library of Science},
reportid = {DZNE-2020-07712},
pages = {e1003346},
year = {2013},
abstract = {Disturbance 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.},
keywords = {ATP-Binding Cassette Transporters: metabolism / Animals /
Caenorhabditis elegans: genetics / Caenorhabditis elegans:
growth $\&$ development / Caenorhabditis elegans: metabolism
/ Caenorhabditis elegans Proteins: genetics / Caenorhabditis
elegans Proteins: metabolism / Cell Nucleus: genetics / Cell
Nucleus: metabolism / Endoplasmic Reticulum: genetics /
Endoplasmic Reticulum: metabolism / JNK Mitogen-Activated
Protein Kinases: genetics / JNK Mitogen-Activated Protein
Kinases: metabolism / Mitochondria: drug effects /
Mitochondria: metabolism / Molecular Chaperones / Paraquat:
pharmacology / Phosphorylation / Protein Folding / Reactive
Oxygen Species: metabolism / Reactive Oxygen Species:
toxicity / Signal Transduction: drug effects / Transcription
Factors: metabolism / Unfolded Protein Response: drug
effects / ATFS-1 protein, C elegans (NLM Chemicals) /
ATP-Binding Cassette Transporters (NLM Chemicals) /
Caenorhabditis elegans Proteins (NLM Chemicals) / HAF-1
protein, C elegans (NLM Chemicals) / Molecular Chaperones
(NLM Chemicals) / Reactive Oxygen Species (NLM Chemicals) /
Transcription Factors (NLM Chemicals) / JNK
Mitogen-Activated Protein Kinases (NLM Chemicals) / KGB-1
protein, C elegans (NLM Chemicals) / Paraquat (NLM
Chemicals)},
cin = {AG Vorberg},
ddc = {610},
cid = {I:(DE-2719)1013004},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:23516373},
pmc = {pmc:PMC3597513},
doi = {10.1371/journal.pgen.1003346},
url = {https://pub.dzne.de/record/141390},
}