(A) Sensitizer BH3-only protein function. A sensitizer BH3-only protein inhibits the antiapoptotic BCL-2 repertoire. Following minimal cellular stress, a direct activator is induced but cannot be inhibited and MOMP proceeds.
(B) Derepressor BH3-only protein function. A direct activator is sequestered by an antiapoptotic BCL-2 protein. Following cellular stress, a derepressor BH3-only protein is induced and competes with the direct activator for binding to the antiapoptotic repertoire. When the direct activator is released, MOMP proceeds.
(C) The neutralization model of BCL-2 family function. In this model, BAK/BAX are always competent to promote MOMP but are actively inhibited by the antiapoptotic BCL-2 repertoire to promote survival. Following cellular stress, BH3-only proteins are induced, bind the antiapoptotic proteins, and displace effectors to promote MOMP.