Q.35 Apoptosis is a controlled process of cell death. The process involves
(A) exposure of phosphatidyl serine on the outer surface of the cell membrane
(B) decreased permeability of the outer mitochondrial membrane
(C) increased lysosomal activity
(D) inter–nucleosomal cleavage of genomic DNA

Apoptosis involves specific hallmarks like exposure of phosphatidylserine and DNA fragmentation. The correct answer is both (A) and (D), as these are key biochemical events in the process. Option (C) relates more to necrosis or autophagy.

Option Analysis

• (A) Exposure of phosphatidylserine: Correct. In early apoptosis, phosphatidylserine flips from the inner to outer leaflet of the plasma membrane via scramblase activation, signaling phagocytes for efferocytosis without inflammation.​

• (B) Decreased permeability of outer mitochondrial membrane: Incorrect. Apoptosis features increased permeability via Bax/Bak pores, releasing cytochrome c to activate caspases.​

• (C) Increased lysosomal activity: Incorrect. Lysosomes destabilize in necrosis or lysosomal cell death, not core apoptosis; apoptosis avoids inflammation.​

• (D) Inter-nucleosomal cleavage of genomic DNA: Correct. Caspase-activated DNase (CAD) causes DNA laddering at 180-200 bp intervals, a hallmark detected by gel electrophoresis.​

Introduction to Apoptosis

The apoptosis process represents controlled cell death essential for development, homeostasis, and disease prevention in multicellular organisms. Unlike necrosis, it avoids inflammation through orderly dismantling by caspases. Key events include phosphatidylserine exposure on the cell membrane and inter-nucleosomal cleavage of genomic DNA.​

Core Mechanisms

Apoptosis proceeds via extrinsic (death receptor) or intrinsic (mitochondrial) pathways, converging on caspase activation. Effector caspases cleave cytoskeletal proteins, causing blebbing and shrinkage. Phosphatidylserine externalization marks cells for phagocytosis early, while DNA fragmentation occurs late.​

• Triggers: Stress, DNA damage, or ligands like FasL.

• Execution: Cytochrome c release forms apoptosome; CAD degrades DNA.

• Detection: Annexin V for membrane changes; TUNEL assay for DNA breaks.

Clinical Relevance

Dysregulated apoptosis links to cancer (evasion), neurodegeneration (excess), and autoimmunity. Therapies target Bcl-2 inhibitors or TRAIL agonists to restore balance. For CSIR NET aspirants, mastering these distinguishes apoptosis from other deaths.​