Abstract

Abstract: Cells are making many decisions during their life, when they select and find nutrients, choose between alternative developmental pathways etc. These decisions are triggered by molecular signals (stimulus) and they are concluded in a change of physiological state. If the decision is irreversible the cellular state reached after the transition is stable even if the initial stimulus is inactivated. Classical examples for irreversible transitions are provided by the eukaryotic cell cycle regulation. In an early stage of the cell cycle, cells can choose between different developmental scenarios: proliferation, quiescence etc. However after passing through a point called ‘Start’ or ‘restriction point’, cells become fully committed for cell division. It is common to explain these irreversible transitions by proteolytic degradation of certain regulatory proteins which is a thermodynamically irreversible process. However this simple and appealing view of irreversible cellular transitions is based on ambiguous notion of ‘irreversibility’. I will argue that the irreversible nature of cellular transitions is a systems-level property of the underlying molecular control network. Therefore irreversibility transition of a molecular control system cannot be attributed to a single molecule or reaction, but derive rather from systems-level feedback signals. This systems-level view of irreversibility is supported by theoretical considerations and by many experimental observations.