​Apoptosis refers to programmed cell death that is triggered by specialized intracellular proteases called caspases. The intrinsic pathway of apoptosis:

A. depends on the activation of the Fas domain by the Fas ligand, which activates the DISC.
B. is regulated by the Bcl2 family of proteins.
C. consists of a key regulatory protein Apaf1, which is a water-soluble component of the electron transport chain.
D. recruits procaspase-9 into the apoptosome, and once activated, caspase-9 cleaves and activates downstream executioner caspases.

Which of the following combinations represents all correct statements?

Correct option is D

​Explanation:

Apoptosis occurs through two main pathways:

1. Extrinsic Pathway (Death Receptor-Mediated)
• Initiated by the binding of death ligands (e.g., Fas ligand) to death receptors (Fas, TNF receptors) on the cell surface.
• Leads to the formation of the Death-Inducing Signaling Complex (DISC), which activates caspase-8, triggering downstream caspase activation.
2. Intrinsic Pathway (Mitochondrial Pathway)
• Regulated by Bcl2 family proteins (e.g., Bcl2, Bax, Bak).
• Involves mitochondrial outer membrane permeabilization (MOMP), leading to cytochrome c release.
• Cytochrome c binds to Apaf1, forming the apoptosome, which activates caspase-9, further activating executioner caspases (caspase-3, -7).

Evaluation of Statements:

• Statement A (Incorrect)
• This describes the extrinsic pathway, where the Fas ligand binds to Fas receptors and activates DISC (Death-Inducing Signaling Complex).
• The intrinsic pathway is not dependent on Fas-FasL interactions.
• Statement B (Correct)
• The intrinsic pathway is tightly regulated by the Bcl2 family of proteins.
• Statement C (Incorrect)
• Apaf1 is indeed a key regulatory protein in the apoptosome.
• However, it is NOT part of the electron transport chain (ETC); instead, cytochrome c is the ETC component released from mitochondria during apoptosis.
• Statement D (Correct)
• Once cytochrome c binds to Apaf1, it forms the apoptosome, which recruits procaspase-9.
• Activated caspase-9 then cleaves and activates executioner caspases (caspase-3, -7), leading to apoptotic cell death.

Thus, the correct answer is (d) B and D only.

Information Booster:

1. Caspases (Cysteine Aspartate Proteases):
• Initiator caspases: Caspase-8 (extrinsic), Caspase-9 (intrinsic)
• Executioner caspases: Caspase-3, Caspase-7
2. Bcl2 Family Proteins:
• Pro-apoptotic: Bax, Bak, Bid
• Anti-apoptotic: Bcl2, Bcl-xL
3. Apoptosome Formation (Intrinsic Pathway):
• Cytochrome c + Apaf1 + ATP → Apoptosome formation
• Procaspase-9 activation → Caspase-9 activation
• Activation of executioner caspases → Apoptosis
4. Extrinsic vs. Intrinsic Apoptosis:
• Extrinsic pathway: Death receptors (Fas, TNF) activate caspase-8 via DISC.
• Intrinsic pathway: Mitochondrial stress leads to cytochrome c release, activating caspase-9.