Intrinsic apoptosis pathway and BH3 profiling. (A) Proapoptotic mitochondrial proteins with BH3-domain only include NOXA (sensitizer), BIM, and PUMA (activators); proapoptotic mitochondrial proteins with multiple domains include BAX and BAK (effectors). Sensitizers and activators suppress (and are suppressed by) antiapoptotic proteins, including BCL-2, BCL-XL, BCL-W, BCL2-A1, and MCL-1. Antiapoptotic proteins also suppress effectors. (B) BH3 profiling exploits the selective binding of BH3 peptides to specific antiapoptotic proteins (adapted from Certo et al).¹⁰