Het intrinsieke apoptotische pad

The intrinsic apoptotic pathway is activated by intracellular death signals, such as oxidative stress and DNA damage.

In mammals, the pathway is regulated by the Bcl-2 family of proteins, which has both pro- and anti-apoptotic family members.

Proapoptotic proteins include BH3-only  proteins, such as Bad and Bim, and effector Bcl-2 family proteins, such as Bax and Bak.  Anti-apoptotic proteins  include Bcl-X_L and Bcl-2  and inhibit Bax and Bak activity.

Death signals activate the BH3-only proteins, which can either inactivate anti-apoptotic proteins or directly bind to effector proteins.

In either case, these effectors oligomerize on the mitochondrial membrane and form pores that release cytochrome c.

Cytochrome c binds to apoptotic protease activating factor-1, Apaf-1, and  Apaf-1 monomers then assemble into a heptameric complex, called the apoptosome.

Next, the initiator procaspase-9 binds to the apoptosome and dimerizes, forming caspase-9.

Finally, caspase-9 activates the executioner caspases that cleave cellular proteins, resulting in apoptosis.