Apoptosis induction via mitochondrial pathway

The mitochondrial pathway of apoptosis, also called the intrinsic apoptosis pathway, describes a regulated process that leads to programmed cell death in response to intracellular stress signals such as DNA damage, oxidative stress, or cytokine withdrawal. Central to this pathway is the permeabilization of the mitochondrial outer membrane (MOMP), controlled by the opposing actions of pro-apoptotic (e.g., BAX, BAK) and anti-apoptotic (e.g., BCL-2, BCL-xL, MCL-1) members of the BCL-2 protein family. Upon MOMP, mitochondrial proteins like cytochrome c and SMAC/DIABLO are released into the cytosol. Cytochrome c binds Apaf-1, forming the apoptosome and activating caspase-9, which in turn activates effector caspases such as caspase-3, irreversibly committing the cell to apoptosis. Dysregulation of this pathway (particularly by overexpression of anti-apoptotic BCL-2 family members) is implicated in cancer cell survival, and targeted drugs ("BH3 mimetics" like venetoclax) have been developed to restore effective apoptosis by antagonizing anti-apoptotic BCL-2 proteins[1][2][4][5][7]. The key druggable molecular targets in this pathway are protein families—not the mitochondrial pathway itself. Examples include BCL-2, BCL-xL, MCL-1 (anti-apoptotic), and BAX, BAK (pro-apoptotic). The entry as provided names a process/pathway, not a molecule; therefore, it should be marked as "incorrect" for structured therapeutic targeting, but detailed pathway and drug information is included above for context[1][2][4][5][7].

Other names

Intrinsic apoptosis pathwayMitochondrial apoptosis pathwayIntrinsic pathway of apoptosisMitochondria-mediated apoptosis

Induction of mitochondrial outer membrane permeabilization (MOMP), Inhibition of anti-apoptotic BCL-2 proteins, Direct activation of BAX/BAK, Disruption of inhibitor of apoptosis proteins (IAP)