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

References in corpus (9)

• Uncovering the overlapping community structure of complex networks in nature and society
• The efficiency of multi-target drugs: the network approach might help drug design
• Cascade control and defense in complex networks
• Efficient routing on complex networks
• Some protein interaction data do not exhibit power law statistics
• Water and molecular chaperones act as weak links of protein folding networks: energy landscape and punctuated equilibrium changes point towards a game theory of proteins
• Topological phase transitions of random networks
• Emergent rewirings for cascades on correlated networks
• Network analysis of protein dynamics

Cited by in corpus (4)

• Creative elements: network-based predictions of active centres in proteins, cellular and social networks
• Chaperones as integrators of cellular networks: Changes of cellular integrity in stress and diseases
• How to design multi-target drugs: Target search options in cellular networks
• Predicting effects of structural stress in a genome-reduced model bacterial metabolism