Nitrogen Regulates AMPK to Control TORC1 Signaling

Cell growth and cell-cycle progression are tightly coordinated to enable cells to adjust their size (timing of division) to the demands of proliferation in varying nutritional environments. In fission yeast, nitrogen stress results in sustained proliferation at a reduced size. Here, we show that cel...

Full description

Saved in:
Bibliographic Details
Published in:Current biology 2015-02, Vol.25 (4), p.445-454
Main Authors: Davie, Elizabeth, Forte, Gabriella M.A., Petersen, Janni
Format: Article
Language:English
Subjects:
Cell Division
Mechanistic Target of Rapamycin Complex 1
Multiprotein Complexes - genetics
Multiprotein Complexes - metabolism
Nitrogen - metabolism
Phosphorylation
Protein Serine-Threonine Kinases - genetics
Protein Serine-Threonine Kinases - metabolism
Schizosaccharomyces - enzymology
Schizosaccharomyces - genetics
Schizosaccharomyces - physiology
Schizosaccharomyces pombe Proteins - genetics
Schizosaccharomyces pombe Proteins - metabolism
Signal Transduction
TOR Serine-Threonine Kinases - genetics
TOR Serine-Threonine Kinases - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cell growth and cell-cycle progression are tightly coordinated to enable cells to adjust their size (timing of division) to the demands of proliferation in varying nutritional environments. In fission yeast, nitrogen stress results in sustained proliferation at a reduced size. Here, we show that cells can sense nitrogen stress to reduce target of rapamycin complex-1 (TORC1) activity. Nitrogen-stress-induced TORC1 inhibition differs from amino-acid-dependent control of TORC1 and requires the Ssp2 (AMPKα) kinase, the Tsc1/2 complex, and Rhb1 GTPase. Importantly, the β and γ regulatory subunits of AMPK are not required to control cell division in response to nitrogen stress, providing evidence for a nitrogen-sensing mechanism that is independent of changes in intracellular ATP/AMP levels. The CaMKK homolog Ssp1 is constitutively required for phosphorylation of the AMPKαSsp2 T loop. However, we find that a second homolog CaMKKPpk34 is specifically required to stimulate AMPKαSsp2 activation in response to nitrogen stress. Finally, ammonia also controls mTORC1 activity in human cells; mTORC1 is activated upon the addition of ammonium to glutamine-starved Hep3B cancer cells. The alternative nitrogen source ammonia can simulate TORC1 activity to support growth and division under challenging nutrient settings, a situation often seen in cancer. [Display omitted] •Nitrogen stress actives AMPK and inhibits TORC1•Nitrogen-stress-induced AMPK activation is independent of its β and γ subunits•Hep3B cells activate mTORC1 in response to increasing ammonium levels•Fission yeast is a model system to study conserved nutrient-sensing pathways Cells adjust their size to varying nutritional environments. Here, Davie et al. show that nitrogen stress activates AMPK to reduce target of rapamycin complex-1 (TORC1) activity. This AMPK activation does not require the β and γ regulatory subunits. Importantly, TORC1 regulation by the alternative nitrogen source ammonia is conserved in human cells.
ISSN:0960-9822
1879-0445
DOI:10.1016/j.cub.2014.12.034