FIGURE 5:

During nutrient stress, upstream sensing mechanisms transduce stress signals to downstream transcription factors. Stress signals can originate from both the extracellular environment and intracellular nutrient reserves. The latter are sensed indirectly via the levels of uncharged tRNAs (in the case of amino acids) or metabolic intermediates that are directly sensed by signaling molecules. The drops in flux through metabolic pathways result in up-regulation of specific biosynthetic pathways and other adaptation responses, indicated in red at the bottom of the figure. Subsequently, metabolic fluxes are remodeled, leading to inactivation of stress responses. This “metabolic feedback,” which is currently not included in our model, determines the long-term responses of the nutrient signaling network.