Figure 1.

Potential Connections Between Apoptosis and Necrosis Signaling in the Mitochondrial Pathway

Apoptosis: BAX and BAK induce permeabilization of the outer mitochondrial membrane (OMM). This allows the release of cytochrome c to the cytosol, where it facilitates assembly of a multiprotein complex called the apoptosome in which caspase activation takes place. Necrosis: Ca²⁺ triggers opening of the permeability transition pore (PTP) in the inner mitochondrial membrane (IMM). This precipitates loss of the IMM proton gradient resulting in cessation of adenosine triphosphate synthesis. Connections: Caspases activated during apoptosis may cleave IMM substrates facilitating PTP opening and secondary necrosis (bolded, dashed, red line). Conversely, PTP opening during primary necrosis may cause mitochondrial swelling and OMM rupture, resulting in cytochrome c release and caspase activation (non-bolded, dashed, red line).