Expression analysis of WT, efk-1, cep-1, and zip-2 mutant C. elegans strains in fed and starved condition

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/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, suggesting that efk-1 promotes survival via a noncanonical pathway. We show that efk-1 upregulates transcription of the 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 a translation-independent pathway. Comparative gene expression profiling (RNA-seq) of N2, efk-1, zip-2 and cep-1 mutant L4 C. elegans hermpahrodites in fed and 8-hour starved conditions