Evaluating bistability of Bax activation switch

Abstract

Mitochondrial apoptotic pathway is precisely controlled by BCL-2 family. Complex interactions of BCL-2 family proteins constitute a bistable switch of which detailed experimental and theoretical delineation remains elusive. In this paper, combined approaches were used to explore the bistability of Bax activation switch. We found that Bax activation is indeed in an 'all-or-none' manner. The 'variable-delay, snap-action' nature for Bax activation is further explored theoretically. We suggest that bistability is largely attributed to topological structure and shows considerable robustness. Therefore, our study characterizes dynamics and sensitivities in intrinsic apoptotic pathway.