Pathology · Advanced Pathology Mechanisms (Multi-topic)

A pathologist studying UV-induced keratinocyte death finds that cytochrome c has been released from mitochondria into the cytosol. Once in the cytosol, cytochrome c initiates the intrinsic apoptotic pathway primarily by:

  • A Directly activating caspase-3 through its proteolytic domain
  • B Inhibiting the Bcl-2 family anti-apoptotic proteins
  • C Binding Apaf-1 to form the apoptosome, which recruits and activates caspase-9
  • D Cleaving Bid to generate truncated tBid
Correct answer: C. Binding Apaf-1 to form the apoptosome, which recruits and activates caspase-9

Explanation

Cytochrome c released from mitochondria binds Apaf-1; the complex oligomerises into the apoptosome, which recruits procaspase-9 through CARD-CARD interactions. Caspase-9 then cleaves and activates executioner caspases 3 and 7. Caspase-3 is activated downstream by caspase-9, not directly by cytochrome c, so A reverses the sequence. Cleavage of Bid by caspase-8 belongs to the extrinsic pathway linking it to mitochondria, not to cytochrome c action.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.

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