2. Academic Validation
  3. Eukaryotic Elongation Factor 2 Kinase EFK-1/eEF2K promotes starvation resistance by preventing oxidative damage in C. elegans

Eukaryotic Elongation Factor 2 Kinase EFK-1/eEF2K promotes starvation resistance by preventing oxidative damage in C. elegans

  • Nat Commun. 2025 Feb 18;16(1):1752. doi: 10.1038/s41467-025-56766-1.
Junran Yan 1 2 3 4,  Forum Bhanshali 1 3 5 6,  Chiaki Shuzenji 1 2 3 5,  Tsultrim T Mendenhall 7,  Shane K B Taylor 1 2 3 5,  Glafira Ermakova 1 2 3 5,  Xuanjin Cheng 1 3 5 8,  Pamela Bai 1 2 3 5,  Gahan Diwan 1 3 9,  Donna Seraj 1 3 5,  Joel N Meyer 10,  Poul H Sorensen 11 12,  Jessica H Hartman 7,  Stefan Taubert 13 14 15 16 17
Affiliations

Affiliations

  • 1 Centre for Molecular Medicine and Therapeutics, The University of British Columbia, 950 W 28 th Ave, Vancouver, BC, V5Z 4H4, Canada.
  • 2 Edwin S.H. Leong Centre for Healthy Aging, The University of British Columbia, 117-2194 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
  • 3 British Columbia Children's Hospital Research Institute, 950 W 28th Ave, Vancouver, BC, V5Z 4H4, Canada.
  • 4 Graduate Program in Cell & Developmental Biology, The University of British Columbia, 950 W 28th Ave, Vancouver, BC, V5Z 4H4, Canada.
  • 5 Department of Medical Genetics, The University of British Columbia, 950 W 28th Ave, Vancouver, BC, V5Z 4H4, Canada.
  • 6 Catalera BioSolutions, 199 W 6th Ave, Vancouver, BC, V5Y 1K3, Canada.
  • 7 Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC, 29425, USA.
  • 8 Canada's Michael Smith Genome Sciences Centre, 570 W 7th Ave, Vancouver, BC, V5Z 4S6, Canada.
  • 9 Department of Biology, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
  • 10 Nicholas School of the Environment, Duke University, Durham, NC, 27708-0328, USA.
  • 11 Department of Pathology and Laboratory Medicine, University of British Columbia, 675 W 10th Ave, Vancouver, BC, V6T 1Z4, Canada.
  • 12 Department of Molecular Oncology, BC Cancer Research Institute, 675 W 10th Ave, Vancouver, BC, V5Z 1L3, Canada.
  • 13 Centre for Molecular Medicine and Therapeutics, The University of British Columbia, 950 W 28 th Ave, Vancouver, BC, V5Z 4H4, Canada. taubert@cmmt.ubc.ca.
  • 14 Edwin S.H. Leong Centre for Healthy Aging, The University of British Columbia, 117-2194 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada. taubert@cmmt.ubc.ca.
  • 15 British Columbia Children's Hospital Research Institute, 950 W 28th Ave, Vancouver, BC, V5Z 4H4, Canada. taubert@cmmt.ubc.ca.
  • 16 Graduate Program in Cell & Developmental Biology, The University of British Columbia, 950 W 28th Ave, Vancouver, BC, V5Z 4H4, Canada. taubert@cmmt.ubc.ca.
  • 17 Department of Medical Genetics, The University of British Columbia, 950 W 28th Ave, Vancouver, BC, V5Z 4H4, Canada. taubert@cmmt.ubc.ca.
PMID: 39966347 DOI: 10.1038/s41467-025-56766-1
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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