Fig. 1. Model for the mechanism of activation of Bak and Bax. In resting cells, Bak is a tail-anchored protein of the mitochondrial outer membrane (MOM) and associates with VDAC2, whereas Bax is loosely attached to mitochondria or sequestered in the cytosol, probably through interactions with retention factors (14-3-3 isoforms , , , ; humanin; Ku70; A- and B-crystallin; Hsp70-dj1 and Hsp70-dj2). Pro168 plays a crucial role both in preventing the inappropriate exposure of the N-terminal domain of Bax and in unleashing the C-terminal tail of Bax from its hydrophobic pocket as it occurs when Bax is activated (Schinzel et al., 2004b). After apoptosis induction, the conformations of Bak and Bax change, leading to exposure of their N-terminal domains and to oligomerization. Apoptogenic factors are then released from the mitochondrial intermembrane space. Several proteins have been suggested to participate in the activation of Bak and Bax, although the mechanisms through which they contribute remain unclear. In addition, some proteins promote apoptosis by inhibiting Bcl-2-like proteins.