Figure 1.

General scheme of apoptotic signaling in mammals. Apoptotic stimuli initiate signaling cascades that converge on the activation of BH3 domain-containing proteins. Activation of these proteins inhibits anti-apoptotic proteins such as Bcl-2, resulting in the oligomerization of the BAK/BAX complex in the outer mitochondrial membrane. BAK/BAX oligomerization forms a pore which allows for the release of cytochrome C into the cytosol, where it nucleates the formation of the Apaf1/caspase-9 apoptosome. The apoptosome catalyzes the activation of executioner caspases (caspase-3, -6, and -7), which are responsible for mediating the disassembly of the apoptosing cell. In addition to driving the degradation of the apoptotic cell, caspase-mediated cleavage also induces PtdSer exposure through the combined inactivation of flippases and the formation of constitutively active scramblases, and also induces the release of “find-me” signals via a variety of mechanisms.