Mitochondrial apoptotic signaling pathway

The mitochondrial apoptotic signaling pathway, also known as the intrinsic pathway, is a fundamental cellular process that regulates programmed cell death in response to internal stressors such as DNA damage or oxidative stress [4]. Central to this machinery is the maintenance of the mitochondrial membrane potential (Δψm), which is often lost during the early stages of apoptosis following mitochondrial outer membrane permeabilization (MOMP) [1]. This process is tightly controlled by the Bcl-2 family of proteins, where a shift in the balance between pro-apoptotic (e.g., Bax, Bak) and anti-apoptotic (e.g., Bcl-2, Bcl-xL) members leads to the release of cytochrome c into the cytosol [2]. Once released, cytochrome c facilitates the formation of the apoptosome and the activation of the caspase cascade, leading to cell death. In cancer, this pathway is frequently evaded through the overexpression of anti-apoptotic proteins, making it a prime target for therapeutic intervention with drugs like Venetoclax [3]. Conversely, preventing the collapse of the mitochondrial membrane potential is a therapeutic goal in treating neurodegenerative and ischemic diseases [1].

Other names

Intrinsic apoptotic pathwayMitochondrial pathway of apoptosisMitochondrial-mediated apoptosis

Drugs typically target specific components of this machinery, such as Bcl-2 family proteins, to either induce or inhibit mitochondrial outer membrane permeabilization (MOMP), thereby controlling the release of pro-apoptotic factors like cytochrome c [2, 4].