The apoptotic arm of the p53 response runs through the mitochondria. In a healthy cell, BAX and BAK are held in check by anti-apoptotic BCL-2-family proteins such as BCL-2, BCL-xL, and MCL-1. When p53 transcribes PUMA and NOXA, these BH3-only proteins bind the anti-apoptotic proteins and displace BAX and BAK. Freed BAX and BAK change conformation, insert into the mitochondrial outer membrane, and assemble into pores. The pores release cytochrome c from the intermembrane space into the cytosol.
Once in the cytosol, cytochrome c binds APAF-1 and, in the presence of dATP or ATP, assembles a heptameric wheel called the apoptosome. The apoptosome recruits procaspase-9 and activates it. Caspase-9 is an initiator caspase; it cleaves and activates the executioner caspases, caspase-3 and caspase-7. These executioner caspases cut a defined set of substrates — nuclear lamins, the inhibitor of CAD (ICAD), and poly(ADP-ribose) polymerase among them — producing the biochemical and morphological changes of apoptosis: chromatin condensation, DNA fragmentation, membrane blebbing, and packaging of the cell into apoptotic bodies that are cleared without inflammation.
The sequence is ordered and irreversible once the mitochondrial pore forms. That is why the BAX/BAK step is often described as the commitment point: upstream signals can be reversed, but once cytochrome c is released, caspase activation proceeds to completion.