On stress signaling, mitochondrial membrane potential dramatically decreases with the formation of a PTPC (associated with VDAC channel), compromising the integrity of the MOM, and spillage of Cyt C into the cytosol. Small molecule inhibitors such as ApoG2, TW-37, AT-101 and ABT-263 bind to the hydrophobic groove of the pro-survival Bcl-2 family members thereby releasing the pro-apoptotic proteins such as Bax. This leads to the formation of mitochondrial membrane channel with concurrent release of Cyt C, resulting in apoptotic cell death.
Cyt C: Cytochrome c; MOM: Mitochondrial outer membrane; PTPC: Permeability transition pore complex.