Response to bistability in apoptosis: roles of bax, Bcl-2,and mitochondrial permeability transition pores

Recently, a mathematical model of the mitochondrial apoptotic pathway was proposed. In that study, the robustness of different simplified signaling models with respect to parameter changes was also investigated. It was found that bistability achieved via cooperative ultrasensitivity is “much more robust” than other mechanisms such as inhibitor ultrasensitivity. We reinvestigate this interesting finding to reveal that it does not hold in such generality. Our results indicate that mechanisms other than cooperative ultrasensitivity, such as inhibitor ultrasensitivity, can confer a similar robust bistable performance. Thereby, these findings are not restricted to apoptosis signaling, but relevant to bistable signaling in general. In addition, example calculations indicate the potential practical relevance of inhibitor ultrasensitivity for generating robustness in apoptosis signaling.