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

Szalay, Máté S.; Kovács, István A.; Korcsmáros, Tamás; Böde, Csaba; Csermely, Péter

doi:10.1016/j.febslet.2007.03.083

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Volume 581, Issue 19 , Pages 3675-3680, 31 July 2007

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

Edited by Robert Barouki

Máté S. Szalay
- Department of Medical Chemistry, Semmelweis University, Puskin str. 9, H-1088 Budapest, Hungary
- Started their research as members of the Hungarian Research Student Association (www.kutdiak.hu), which provides research opportunities for talented high school students since 1996.
István A. Kovács
- Department of Medical Chemistry, Semmelweis University, Puskin str. 9, H-1088 Budapest, Hungary
- Started their research as members of the Hungarian Research Student Association (www.kutdiak.hu), which provides research opportunities for talented high school students since 1996.
Tamás Korcsmáros
- Department of Medical Chemistry, Semmelweis University, Puskin str. 9, H-1088 Budapest, Hungary
- Started their research as members of the Hungarian Research Student Association (www.kutdiak.hu), which provides research opportunities for talented high school students since 1996.
Csaba Böde
- Department of Biophysics and Radiation Biology, Semmelweis University, Puskin str. 9, H-1088 Budapest, Hungary
- Started their research as members of the Hungarian Research Student Association (www.kutdiak.hu), which provides research opportunities for talented high school students since 1996.
Péter Csermely
- Department of Medical Chemistry, Semmelweis University, Puskin str. 9, H-1088 Budapest, Hungary
- Corresponding author. Present address: Department of Medical Chemistry, Semmelweis University School of Medicine, P.O. Box 260, H-1444 Budapest, Hungary. Fax: +36 1 266 6550.

Received 4 February 2007; received in revised form 12 March 2007; accepted 31 March 2007. published online 11 April 2007.

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.

Keywords: Ageing, Chaperone, Complex systems, Hubs, Learning, Network dynamics, Network modules, Stress