In the intrinsic apoptotic pathway, cytochrome c released from mitochondria forms the apoptosome. The direct molecular function of the apoptosome is:

• A Inserting perforins into the target cell plasma membrane
• B Activating procaspase-8 via DISC (death-inducing signalling complex) formation
• C Releasing AIF (apoptosis-inducing factor) from the endoplasmic reticulum
• D Forming a heptameric Apaf-1/cytochrome c/dATP complex that activates procaspase-9 ✓

Explanation

Upon mitochondrial outer membrane permeabilisation (MOMP) driven by BAX/BAK activation, cytochrome c is released into the cytoplasm. Cytochrome c binds Apaf-1 (apoptotic protease-activating factor 1) in the presence of dATP/ATP, causing Apaf-1 to undergo conformational change and oligomerise into a heptameric wheel-like structure called the apoptosome. The apoptosome recruits and activates procaspase-9 (the initiator caspase of the intrinsic pathway), which then cleaves and activates effector caspases-3 and -7. Perforins are used by cytotoxic T cells and NK cells; caspase-8 activation via DISC belongs to the extrinsic (death receptor) pathway; AIF is a caspase-independent mediator and is not released from the ER.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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