  Interactions between individual members of the B-cell lymphoma 2 (Bcl-2)
family of proteins form a regulatory network governing mitochondrial outer
membrane permeabilization (MOMP). Bcl-2 family initiated MOMP causes release of
the inter-membrane pro-apoptotic proteins to cytosol and creates a cytosolic
environment suitable for the executionary phase of apoptosis. Using
mathematical modeling and computational simulation, we have analyzed the
response of this regulatory network caused by the up-/downregulation of each
individual member of the Bcl-2 family. As a result, a non-linear
stimulus-response emerged, the characteristics of which are associated with
bistability and switch-like behavior. Using the principal component analysis
(PCA) we have shown that the Bcl-2 family classifies the random combinations of
inputs into two distinct classes, and responds to these by one of the two
qualitatively distinct outputs. As we showed, the emergence of this behavior
requires specific organization of the interactions between particular Bcl-2
proteins.
