Mitochondrial intrinsic apoptosis pathway (Intrinsic apoptosis pathway)

The mitochondrial intrinsic apoptosis pathway is a fundamental mechanism of programmed cell death triggered by internal cellular stressors such as DNA damage, hypoxia, or metabolic stress [1]. This pathway is primarily regulated by the B-cell lymphoma 2 (BCL-2) family of proteins, which control the integrity of the mitochondrial outer membrane [2]. Upon activation, pro-apoptotic proteins like BAX and BAK induce Mitochondrial Outer Membrane Permeabilization (MOMP), leading to the release of cytochrome c and other pro-apoptotic factors into the cytoplasm [3]. These factors facilitate the assembly of the apoptosome and the activation of initiator caspase-9, which subsequently activates executioner caspases like caspase-3 to dismantle the cell [1, 4]. In many cancers, the pathway is inhibited by the overexpression of anti-apoptotic proteins (e.g., BCL-2, MCL-1), making it a critical focus for therapeutic intervention using BH3 mimetics like venetoclax [2]. Restoration of this pathway is a key strategy in treating hematologic malignancies and overcoming resistance to conventional chemotherapy [2, 3].

Other names

Intrinsic apoptotic signaling pathwayBCL-2 regulated apoptosis pathwayMitochondrial pathway of apoptosisIntrinsic programmed cell death

Inhibition of anti-apoptotic BCL-2 family proteins (such as BCL-2, BCL-XL, or MCL-1) to facilitate Mitochondrial Outer Membrane Permeabilization (MOMP), leading to cytochrome c release and caspase cascade activation.