Apoptosis (Programmed Cell Death)

Overview

• Apoptosis, or programmed cell death, is a natural process that occurs in the cells of our body and other organisms.
• Apoptosis involves a series of reactions that lead to cell death, also known as cell suicide.

Reasons for Apoptosis

1. Embryological Development:
   • Forms fingers by eliminating cells between finger regions.
   • Normal part of immune system development.
2. Prevent Harm to Other Cells:
   • Destroys cells that can harm healthy cells, e.g., cancer cells, infected cells, or damaged cells.

Mechanisms of Apoptosis

1. Intrinsic Pathway

   • Initiated inside the cell, specifically in the mitochondria.
   • Steps:
     1. Cell damage leads to Bax protein production.
     2. Bax attaches to mitochondria membrane next to Bcl-2.
     3. Bax punctures the membrane, releasing cytochrome C.
     4. Cytochrome C binds to Apaf-1, forming apoptosome.
     5. Apoptosome activates caspase-9.
     6. Caspase-9 complex breaks down organelles and DNA.
     7. Macrophages engulf the cell remains.

2. Extrinsic Pathway

   • Initiated outside the cell.
   • Steps:
     1. Death receptors on cell membrane bind to death activators from external sources, e.g., immune cells like cytotoxic T cells.
     2. Binding activates caspase-8 inside the cell.
     3. Caspase-8 destroys organelles and DNA.
     4. Macrophages engulf the cell remains.

3. Apoptosis Inducing Factor (AIF) Pathway

   • Does not involve caspases.
   • Steps:
     1. AIF is released from the mitochondrial intermembrane space when cell damage occurs.
     2. AIF travels to the nucleus and binds to DNA.
     3. AIF destroys the DNA.

Key Proteins and Molecules

• Bcl-2: Inhibits apoptosis in healthy cells.
• Bax: Promotes apoptosis by puncturing the mitochondrial membrane.
• Cytochrome C: Released during intrinsic pathway, forms apoptosome with Apaf-1.
• Apaf-1: Binds with Cytochrome C to form apoptosome.
• Caspase-9: Activated in the intrinsic pathway to break down cell components.
• Caspase-8: Activated in the extrinsic pathway to break down cell components.
• AIF (Apoptosis Inducing Factor): Initiates DNA destruction in cells, especially neurons, without involving caspases.

Summary

• Apoptosis is a crucial process in development and maintaining cellular health by eliminating harmful or unnecessary cells.
• It can be triggered internally through mitochondrial signals, externally through death receptor signals, or through the action of AIF.
• Understanding these pathways can provide insights into treatments for conditions like cancer and autoimmune diseases.