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

Abstract

Cells and organisms frequently experience starvation. To adapt and 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 responds to starvation by phosphorylating and inactivating the translation elongation driver eEF2, thus shutting down translation and facilitating survival.C. elegans efk-1/eEF2Kphosphorylates 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 starvedC. elegans, suggesting thatefk-1promotes survival via a noncanonical pathway. We show thatefk-1upregulates transcription of the DNA repair pathways, nucleotide excision repair (NER) and base excision repair (BER), to promote starvation survival. Furthermore,efk-1suppresses oxygen consumption and ROS production in starvation to prevent oxidative stress. Thus,efk-1enables starvation survival by protecting animals from starvation-induced oxidative damage through a translation-independent pathway.