The indirect activator model and the direct activator-derepressor model. In the indirect activator model, activation of BAX and BAK can be directly suppressed by any of the antiapoptotic BCL-2 family proteins. Upon apoptotic stimuli, BH3-only proteins are induced and occupy the antiapoptotic BCL-2 family proteins, which will release BAX and BAK to form active pore-forming oligomers. In the direct activator-derepressor model, the activation of BAX/BAK is prevented by the suppression of BH3-only proteins by the antiapoptotic BCL-2 family proteins. Upon induction of BH3-only proteins, derepressors (e.g., BAD and NOXA) competitively bind to antiapoptotic BCL-2 family proteins (e.g., BID, BIM, PUMA), which will release direct activators and allow for subsequent oligomerization of BAX and BAK.