RRC ID 84195
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.
Title Eukaryotic Elongation Factor 2 Kinase EFK-1/eEF2K promotes starvation resistance by preventing oxidative damage in C. elegans.
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.
Volume 16(1)
Pages 1752
Published 2025-2-18
DOI 10.1038/s41467-025-56766-1
PII 10.1038/s41467-025-56766-1
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