RRC ID |
84195
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Author |
Yan J, Bhanshali F, Shuzenji C, Mendenhall TT, Taylor SKB, Ermakova G, Cheng X, Bai P, Diwan G, Seraj D, Meyer JN, Sorensen PH, Hartman JH, Taubert S.
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Title |
Eukaryotic Elongation Factor 2 Kinase EFK-1/eEF2K promotes starvation resistance by preventing oxidative damage in C. elegans.
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Journal |
Nat Commun
|
Abstract |
Cells and organisms frequently experience starvation. To survive, they mount an evolutionarily conserved stress response. A vital component in the mammalian starvation response is eukaryotic elongation factor 2 (eEF2) kinase (eEF2K), which suppresses translation in starvation by phosphorylating and inactivating the translation elongation driver eEF2. C. elegans EFK-1/eEF2K phosphorylates EEF-2/eEF2 on a conserved residue and is required for starvation survival, but how it promotes survival remains unclear. Surprisingly, we found that eEF2 phosphorylation is unchanged in starved C. elegans and EFK-1's kinase activity is dispensable for starvation survival, suggesting that efk-1 promotes survival via a noncanonical pathway. We show that efk-1 upregulates transcription of DNA repair pathways, nucleotide excision repair (NER) and base excision repair (BER), to promote starvation survival. Furthermore, efk-1 suppresses oxygen consumption and ROS production in starvation to prevent oxidative stress. Thus, efk-1 enables starvation survival by protecting animals from starvation-induced oxidative damage through an EEF-2-independent pathway.
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Volume |
16(1)
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Pages |
1752
|
Published |
2025-2-18
|
DOI |
10.1038/s41467-025-56766-1
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PII |
10.1038/s41467-025-56766-1
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PMID |
39966347
|
PMC |
PMC11836464
|
MeSH |
Animals
Caenorhabditis elegans* / genetics
Caenorhabditis elegans* / metabolism
Caenorhabditis elegans Proteins* / genetics
Caenorhabditis elegans Proteins* / metabolism
DNA Repair / genetics
Elongation Factor 2 Kinase* / genetics
Elongation Factor 2 Kinase* / metabolism
Oxidative Stress*
Phosphorylation
Reactive Oxygen Species / metabolism
Starvation* / metabolism
|
Resource |
C.elegans |
tm6691
tm3886
tm1670
tm6641
tm4539
tm4248
tm1682
tm4374
tm4063
tm2862
tm1981
tm2842
tm6991
tm5421 |