Cancer cell apoptosis via mitochondrial depolarization

The term "cancer cell apoptosis via mitochondrial depolarization" refers to the intrinsic apoptotic pathway, which is triggered by internal cellular stressors such as DNA damage, oxidative stress, hypoxia, or chemotherapeutic agents. This leads to activation and oligomerization of pro-apoptotic Bcl‐2 family proteins like Bax and Bak at the mitochondria. These events disrupt outer mitochondrial membrane permeability—sometimes accompanied by loss ("depolarization") of inner transmembrane potential (ΔΨ_m)—and result in release of intermembrane space factors like cytochrome c into the cytosol. Cytochrome c then binds Apaf‐1 forming an “apoptosome,” which activates initiator caspase‐9 followed by effector caspases such as caspase‐3/7/6 that execute cellular demolition characteristic of programmed cell death[1][4]. While loss of ΔΨ_m often accompanies these events and serves as an experimental marker for early-stage intrinsic apoptosis,[5] it may not be strictly required for all forms/cell types undergoing mitochondria-mediated death.[4] Dysregulation at any step can contribute significantly to cancer development/progression and resistance against anticancer therapies.[1]

Other names

Mitochondria-mediated apoptosisIntrinsic apoptotic pathwayMitochondrial membrane potential loss-induced apoptosis

Drugs targeting this process typically: - Induce stress signals leading to activation of pro-apoptotic Bcl-2 family members (Bax/Bak) - Cause permeabilization/depolarization of the mitochondrial outer membrane - Promote release of cytochrome c into cytosol → formation of apoptosome → activation of caspase cascade → execution phase of apoptosis