intrinsic apoptotic pathway
/ in-TRIN-sik ay-pop-TOH-tik /
Picture a building with its own internal alarm system: if the sensors inside detect a fire, a burst pipe, or structural damage, the building decides on its own to shut down — no call from outside required. Cells have a similar self-monitoring system for deciding to die. When the trouble comes from inside the cell, the death program it triggers is called the intrinsic apoptotic pathway. Because the decision is made at the mitochondria, it is also called the mitochondrial pathway.
The pathway works by reading the cell's own state of health. Internal stresses — irreparable DNA damage, lack of survival signals, severe oxidative stress, or buildup of misfolded proteins — tip a balance between two opposing groups of proteins in the Bcl-2 family. Pro-survival members normally guard the mitochondria; pro-death members (such as Bax and Bak) push to open them. When death wins, Bax and Bak punch pores in the outer mitochondrial membrane, and a small protein called cytochrome c spills out into the cytoplasm. Cytochrome c teams up with a protein called Apaf-1 to build the apoptosome, a wheel-shaped platform that activates initiator caspase-9, which in turn unleashes the executioner caspases that dismantle the cell.
This pathway is the cell's quality-control backstop, and the tumor-suppressor protein p53 is one of its chief triggers: when p53 senses unfixable DNA damage, it can switch on pro-death genes and steer the cell into intrinsic apoptosis rather than let a dangerous cell survive. Many cancers disable this pathway — for example by silencing p53 or overproducing pro-survival Bcl-2 — which is exactly why those cells keep living when they should die. The other major route, the extrinsic pathway, starts instead from signals arriving at the cell surface.
Radiation therapy deliberately damages a tumor cell's DNA beyond repair. The cell's p53 protein detects the damage and switches on pro-death Bcl-2-family proteins. Bax punches pores in the mitochondria, cytochrome c leaks out, the apoptosome forms, and the cell self-destructs through the intrinsic pathway — which is part of how radiation kills cancer cells.
Internal damage opens the mitochondria, releasing cytochrome c and triggering self-destruction.
'Intrinsic' refers to the trigger coming from inside the cell, not to the mitochondria having a death wish. Mitochondria are mainly power plants; their role here is to act as the gatekeeper that, once opened, commits the cell to die.