Intrinsic mitochondrial apoptotic pathway

The intrinsic mitochondrial apoptotic pathway is a fundamental mechanism of programmed cell death triggered by internal cellular signals such as DNA damage, hypoxia, or metabolic stress [1]. This pathway is strictly regulated by the BCL-2 family of proteins, which maintain a delicate balance between pro-apoptotic members like BAX and BAK and anti-apoptotic members like BCL-2, BCL-XL, and MCL-1 [2]. When pro-apoptotic signals predominate, BAX and BAK undergo oligomerization to induce mitochondrial outer membrane permeabilization (MOMP), leading to the release of cytochrome c into the cytosol [3]. Once released, cytochrome c facilitates the formation of the apoptosome, which activates the initiator caspase-9 and subsequent executioner caspases to dismantle the cell [1][3]. Dysregulation of this pathway is a hallmark of many cancers, where the overexpression of anti-apoptotic proteins allows malignant cells to evade death despite oncogenic stress [2]. Therapeutic strategies often utilize BH3 mimetics, such as Venetoclax, to inhibit anti-apoptotic proteins and restore the cell's natural ability to undergo apoptosis [4].

Other names

Mitochondrial pathway of apoptosisBCL-2-regulated apoptotic pathwayIntrinsic apoptotic signaling pathwayStress-induced apoptotic pathway

Induction of apoptosis by inhibiting anti-apoptotic BCL-2 family proteins (e.g., BCL-2, MCL-1), thereby triggering mitochondrial outer membrane permeabilization (MOMP), cytochrome c release, and activation of the caspase cascade [1][2][4].