Adaptive Benefits of Storage Strategy and dual AMPK/TOR Signaling in Metabolic Stress Response
Résumé
Cellular metabolism must ensure that supply of nutrient meets the biosynthetic and
bioenergetic needs. Cells have therefore developed sophisticate signaling and
regulatory pathways in order to cope with dynamic fluctuations of both resource and
demand and to regulate accordingly diverse anabolic and catabolic processes.
Intriguingly, these pathways are organized around a relatively small number of
regulatory hubs, such as the highly-conserved AMPK and TOR kinase families in
eukaryotic cells. Here, the global metabolic adaptations upon dynamic environment are
investigated using a prototypical model of regulated metabolism. In this model, the
optimal enzyme profile as well as the underlying regulatory architecture are identified
by combining perturbation and evolutionary methods. The results reveal the existence
of distinct classes of adaptive strategies, which differ in the management of storage
reserve depending on the intensity of the stress and in the regulation of ATP-producing
reaction depending on the nature of the stress. The regulatory architecture that
optimally implements these adaptive features is characterized by a crosstalk between
two specialized signaling pathways, which bears close similarities with the sensing and
regulatory properties of AMPK and TOR pathways.
Domaines
Sciences du Vivant [q-bio]
Origine : Fichiers produits par l'(les) auteur(s)
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