Cell death A dynamic response concept

Autophagy, apoptosis and necrosis have previously been described as distinct static processes that induce and execute cell death. Due to an increased use of novel techniques in mapping cellular death-techniques which allow for reporting of real-time data-the existence of grey zones between cell death modes and the existence of the point of no return within these have been revealed. This revelation demands the integration of new concepts in describing the cellular death process. Furthermore, since the contribution of autophagy in cell death or cell survival is still poorly understood, it is important to accurately describe its function within the dynamic framework of cell death. In this review cell death is viewed as a dynamic and integrative cellular response to ensure the highest likelihood of self-preservation. Suggestions are offered for conceptualizing cell death modes and their morphological features, both individually and in relation to one another. It addresses the need for distinguishing between dying cells and dead cells so as to better locate and control the onset of cell death. Most importantly, the fundamental role of autophagy, autophagic flux, and the effects of the intracellular metabolic environment on the kinetics of the cell death modes are stressed. It also contextualizes the kinetic dimension of cell death as a process and aims to contribute towards a better understanding of autophagy as a key mechanism within this process. Understanding the dynamic nature of the cell death process and autophagy's central role can reveal new insight for therapeutic intervention in preventing cell death.