The general control nonderepressible-2 kinase mediates stress response and longevity induced by target of rapamycin inactivation in Caenorhabditis elegans
Article first published online: 28 JUN 2013
© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 12, Issue 5, pages 742–751, October 2013
How to Cite
Rousakis, A., Vlassis, A., Vlanti, A., Patera, S., Thireos, G. and Syntichaki, P. (2013), The general control nonderepressible-2 kinase mediates stress response and longevity induced by target of rapamycin inactivation in Caenorhabditis elegans. Aging Cell, 12: 742–751. doi: 10.1111/acel.12101
- Issue published online: 11 SEP 2013
- Article first published online: 28 JUN 2013
- Accepted manuscript online: 20 MAY 2013 09:16AM EST
- Manuscript Accepted: 8 APR 2013
- European Research Council. Grant Number: FP/2007-2013
- ERC. Grant Number: 201975
- general control nonderepressible 2;
- target of rapamycin;
- Caenorhabditis elegans ;
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.