A cell undergoes apoptosis via the intrinsic (mitochondrial) pathway. The key initiating event is:

• A Activation of death receptors (FAS/FASL) on the cell surface
• B Granzyme B delivery by cytotoxic T lymphocytes
• C Increased mitochondrial outer membrane permeability with cytochrome c release into cytosol ✓
• D Direct activation of caspase-8 by TRADD-FADD complex

Explanation

The intrinsic pathway is triggered by cellular stress (DNA damage, oxidative stress, growth factor withdrawal), leading to BAX/BAK-mediated mitochondrial outer membrane permeabilization. Released cytochrome c forms the apoptosome with APAF-1 and pro-caspase-9, activating downstream executioner caspases. FAS/FASL and granzyme B are extrinsic pathway triggers. Caspase-8 activation via TRADD-FADD is the extrinsic pathway.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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