Question

Following events occur during apoptosis
A. Certain proteins are released, which are contained between the inner mitochondrial membrane and outer mitochondrial membrane (eg., Cytochrome C)
B. Which causes the destruction of cellular proteins.
C. This activates caspase 9
D. Apoptotic signals carried through FADD activates caspase 8, which targets mitochondria.
E. The result is cell death by apoptosis.
Choose the correct sequence from the options given below:

• A. A, C, D, E, B
• B. B, E, D, C, A
• C. D, A, C, B, E
• D. C, E, B, D, A

Hint:

Apoptosis Cascade: FADD/Caspase-8 (D) $\rightarrow$ Cytochrome C Release (A) $\rightarrow$ Apoptosome/Caspase-9 (C) $\rightarrow$ Executioner Caspases destroy proteins (B) $\rightarrow$ Apoptotic Death (E).

Answer 1

The Correct Option is C

Step 1: Understanding the Concept:
Extrinsic (death receptor) and intrinsic (mitochondrial) apoptosis signaling pathways converge through initiator caspases, mitochondrial outer membrane permeabilization, and executioner caspase cascades.

Step 2: Detailed Explanation:
The chronological biochemical cascade of apoptosis:
1. Step 1 (D): Death receptor ligation recruits FADD adaptor protein, activating initiator Caspase-8, which cleaves Bid into tBid to target and permeabilize mitochondria.
2. Step 2 (A): Mitochondrial outer membrane permeabilization releases pro-apoptotic intermembrane space proteins, primarily Cytochrome C, into the cytosol.
3. Step 3 (C): Cytosolic Cytochrome C binds Apaf-1 and dATP to assemble the apoptosome, which recruits and activates Caspase-9.
4. Step 4 (B): Active Caspase-9 proteolytically activates downstream executioner Caspases-3 and 7, which cause mass destruction and cleavage of structural/cellular proteins (ICAD, lamins, PARP).
5. Step 5 (E): The final culmination is organized cell death by apoptosis.
Sequence: D $\rightarrow$ A $\rightarrow$ C $\rightarrow$ B $\rightarrow$ E.

Step 3: Final Answer:
Therefore, the correct sequence is D, A, C, B, E, corresponding to option (C).