Schematic presentation of the mitochondrial apoptotic pathway with indication of the targets of some prominent BH3 mimetic drugs. The mitochondrial apoptosis pathway is triggered upon intracellular stress, such as cytokine deprivation, DNA damage or oncogene activation, which results in the activation of pro-apoptotic BH3-only proteins through transcriptional and/or post-transcriptional processes. BH3-only proteins bind and neutralise the pro-survival BCL-2 proteins, thereby unleashing the apoptosis effectors, BAX and BAK, which in healthy cells are restrained by the pro-survival BCL-2 proteins. The activation of BAX and/or BAK results in mitochondrial outer membrane permeabilisation (MOMP) and consequently apoptotic cell death. Some BH3-only proteins can reportedly also directly bind and activate BAX and BAK. The figure also shows some prominent BH3 mimetic drugs, such as the BCL-2 specific inhibitor Venetoclax, indicating the pro-survival BCL-2 family members that they target selectively.
- Kerstin Brinkmann
- Ashley P. Ng
- Andreas Strasser