FIGURE 4.

Direct and indirect mechanism models for Bax or Bak activation in the intrinsic cell death pathway. In the indirect activation model (left), in the resting state effectors Bax and Bak are inhibited directly by pro-survival members (1). After an apoptotic stimulus, BH3-only proteins bind to pro-survival proteins releasing pre-activated Bak and Bax (2) to initiate the apoptosis process (3). In the direct activation model (right), after an apoptotic stimulus BH3-only activators activate Bak/Bax, whereas BH3-sensitizers inhibit pro-survival Bcl-2 members, initiating the apoptotic process.