Eukaryotic Elongation Factor 2 Kinase EFK-1/eEF2K promotes starvation resistance by preventing oxidative damage in C. elegans
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.
Authors
- Glafira Ermakova
- Joel N. Meyer (ORCID: https://orcid.org/0000-0003-1219-0983)
- Xuanjin Cheng (ORCID: https://orcid.org/0000-0002-2119-1788)
- Junran Yan (ORCID: https://orcid.org/0009-0003-6793-123X)
- Shane K. B. Taylor (ORCID: https://orcid.org/0000-0003-4904-4314)
- Stefan Taubert (ORCID: https://orcid.org/0000-0002-2432-7257)
- Poul H. Sorensen (ORCID: https://orcid.org/0000-0001-7447-2199)
- Pamela Bai (ORCID: https://orcid.org/0009-0005-5075-7663)
- Forum Bhanshali (ORCID: https://orcid.org/0000-0002-0571-9263)
- Chiaki Shuzenji
- Tsultrim T. Mendenhall (ORCID: https://orcid.org/0009-0006-2009-9070)
- Gahan Diwan (ORCID: https://orcid.org/0009-0006-8306-2750)
- Donna Seraj
- Jessica H. Hartman (ORCID: https://orcid.org/0000-0002-9134-7469)
Institutions
- University of British Columbia (CA)
- Medical University of South Carolina (US)
- Duke University (US)
- Canada's Michael Smith Genome Sciences Centre (CA)
- Emergent BioSolutions (Canada) (CA)
- BC Children's Hospital (CA)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-02-18
- DOI
- https://doi.org/10.1038/s41467-025-56766-1
- Citations
- 6
- Primary Topic
- Genetics, Aging, and Longevity in Model Organisms
- Type
- article
- Field-Weighted Citation Impact
- 5.72
Funders
- Conquer Cancer Foundation
- Roswell Park Cancer Institute
- BC Children’s Hospital Foundation
- Faculty of Medicine, University of British Columbia
- BC Children's Hospital
- Kwantlen Polytechnic University
- Universities Space Research Association
- Canada Research Chairs
- National Institutes of Health
- University of California, San Diego
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- BC Cancer Agency