TY  - JOUR
AU  - Runkel, Eva D
AU  - Liu, Shu
AU  - Baumeister, Ralf
AU  - Schulze, Ekkehard
TI  - Surveillance-activated defenses block the ROS-induced mitochondrial unfolded protein response.
JO  - PLoS Genetics
VL  - 9
IS  - 3
SN  - 1553-7404
CY  - San Francisco, Calif.
PB  - Public Library of Science
M1  - DZNE-2020-07712
SP  - e1003346
PY  - 2013
AB  - 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.
KW  - ATP-Binding Cassette Transporters: metabolism
KW  - Animals
KW  - Caenorhabditis elegans: genetics
KW  - Caenorhabditis elegans: growth & development
KW  - Caenorhabditis elegans: metabolism
KW  - Caenorhabditis elegans Proteins: genetics
KW  - Caenorhabditis elegans Proteins: metabolism
KW  - Cell Nucleus: genetics
KW  - Cell Nucleus: metabolism
KW  - Endoplasmic Reticulum: genetics
KW  - Endoplasmic Reticulum: metabolism
KW  - JNK Mitogen-Activated Protein Kinases: genetics
KW  - JNK Mitogen-Activated Protein Kinases: metabolism
KW  - Mitochondria: drug effects
KW  - Mitochondria: metabolism
KW  - Molecular Chaperones
KW  - Paraquat: pharmacology
KW  - Phosphorylation
KW  - Protein Folding
KW  - Reactive Oxygen Species: metabolism
KW  - Reactive Oxygen Species: toxicity
KW  - Signal Transduction: drug effects
KW  - Transcription Factors: metabolism
KW  - Unfolded Protein Response: drug effects
KW  - ATFS-1 protein, C elegans (NLM Chemicals)
KW  - ATP-Binding Cassette Transporters (NLM Chemicals)
KW  - Caenorhabditis elegans Proteins (NLM Chemicals)
KW  - HAF-1 protein, C elegans (NLM Chemicals)
KW  - Molecular Chaperones (NLM Chemicals)
KW  - Reactive Oxygen Species (NLM Chemicals)
KW  - Transcription Factors (NLM Chemicals)
KW  - JNK Mitogen-Activated Protein Kinases (NLM Chemicals)
KW  - KGB-1 protein, C elegans (NLM Chemicals)
KW  - Paraquat (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:23516373
C2  - pmc:PMC3597513
DO  - DOI:10.1371/journal.pgen.1003346
UR  - https://pub.dzne.de/record/141390
ER  -