Stress-induced rearrangements of cellular networks: consequences for protection and drug design

Abstract

The complexity of the cells can be described and understood by a number of networks such as protein-protein interaction, cytoskeletal, organelle, signalling, gene transcription and metabolic networks. All these networks are highly dynamic producing continuous rearrangements in their links, hubs, network-skeleton and modules. Here we describe the adaptation of cellular networks after various forms of stress causing perturbations, congestions and network damage. Chronic stress decreases link-density, decouples or even quarantines modules, and induces an increased competition between network hubs and bridges. Extremely long or strong stress may induce a topological phase transition in the respective cellular networks, which switches the cell to a completely different mode of cellular function. We summarize our initial knowledge on network restoration after stress including the role of molecular chaperones in this process. Finally, we discuss the implications of stress-induced network rearrangements in diseases and ageing, and propose therapeutic approaches both to increase the robustness and help the repair of cellular networks.

9 pages, 1 table, 2 figures, invited paper of FEBS Letters Cellular Stress special issue

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• Category theoretic analysis of hierarchical protein materials and social networks
• Heat shock partially dissociates the overlapping modules of the yeast protein-protein interaction network: a systems level model of adaptation
• Ageing as a price of cooperation and complexity: Self-organization of complex systems causes the ageing of constituent networks
• System level mechanisms of adaptation, learning, memory formation and evolvability: the role of chaperone and other networks
• How to design multi-target drugs: Target search options in cellular networks
• Network modules help the identification of key transport routes, signaling pathways in cellular and other networks
• Predicting effects of structural stress in a genome-reduced model bacterial metabolism