Modeling of the Effect of Crosstalk in Apoptotic Pathways on Caspase-3 Activation

Apoptosis is a physiologically crucial process for the control of cellular development and homeostasis in multi-cellular organisms. It occurs as a result of signal cascades in a complex cellular network. Although individual apoptotic signal pathways have been revealed, it is difficult to explain the effect of collaborative responses in apoptosis system. In the present work, we propose a mathematical model for crosstalk between the death receptor and the mitochondria-dependent pathway. The crosstalk in this model is a key element to ensure bistability, an important feature for the completion of apoptotic events. Our analysis suggests that the crosstalk between positive feedback loops in two major apoptotic pathways can perform an important role in terms of maintaining bistability. We show that the crosstalk can enhance feedback strength, leading to irreversible caspase-3 activation.