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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Aris Rousakis
  • Arsenios Vlassis
  • Anna Vlanti
  • Stefania Patera
  • George Thireos
  • Popi Syntichaki

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.

Original languageEnglish
JournalAging Cell
Volume12
Issue number5
Pages (from-to)742-51
Number of pages10
ISSN1474-9718
DOIs
Publication statusPublished - Oct 2013
Externally publishedYes

    Research areas

  • Activating Transcription Factors, Amino Acid Sequence, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Eukaryotic Initiation Factor-2, Gene Expression, Longevity, Male, Molecular Sequence Data, Phosphorylation, Protein Kinases, Signal Transduction, Stress, Physiological, TOR Serine-Threonine Kinases

ID: 117691643