The general control nonderepressible-2 kinase mediates stress response and longevity induced by target of rapamycin inactivation in Caenorhabditis elegans

Authors

  • Aris Rousakis,

    1. Biomedical Research Foundation of the Academy of Athens, Center of Basic Research II, Athens, Greece
    2. School of Medicine, University of Athens, Athens, Greece
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  • Arsenios Vlassis,

    1. Biomedical Research Foundation of the Academy of Athens, Center of Basic Research II, Athens, Greece
    2. Faculty of Biology, University of Athens, Athens, Greece
    Current affiliation:
    1. Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen 2200, Denmark
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  • Anna Vlanti,

    1. Biomedical Research Foundation of the Academy of Athens, Center of Basic Research II, Athens, Greece
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  • Stefania Patera,

    1. Biomedical Research Foundation of the Academy of Athens, Center of Basic Research II, Athens, Greece
    2. School of Medicine, University of Athens, Athens, Greece
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  • George Thireos,

    1. Biomedical Research Foundation of the Academy of Athens, Center of Basic Research II, Athens, Greece
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  • Popi Syntichaki

    Corresponding author
    • Biomedical Research Foundation of the Academy of Athens, Center of Basic Research II, Athens, Greece
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Correspondence

Popi Syntichaki, Biomedical Research Foundation of the Academy of Athens, Center of Basic Research II, 4 Soranou Ephessiou, 11527 Athens, Greece. Tel.: +302106597474; fax: +302106597545; e-mail: synticha@bioacademy.gr

Summary

The general control nonderepressible 2 (GCN2) kinase is a nutrient-sensing pathway that responds to amino acids deficiency and induces a genetic program to effectively maintain cellular homeostasis. Here we established the conserved role of Caenorhabditis elegans GCN-2 under amino acid limitation as a translation initiation factor 2 (eIF2) kinase. Using a combination of genetic and molecular approaches, we showed that GCN-2 kinase activity plays a central role in survival under nutrient stress and mediates lifespan extension conferred by dietary restriction (DR) or inhibition of the major nutrient-sensing pathway, the target of rapamycin (TOR). We also demonstrated that the GCN-2 and TOR signaling pathways converge on the PHA-4/FoxA transcription factor and its downstream target genes to ensure survival of the whole organism under a multitude of stress conditions, such as nutrient scarcity or environmental stresses. This is one step forward in the understanding of evolutionary conserved mechanisms that confer longevity and healthspan.

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