46. Programmed cell death, apoptosis and necrosis. Main mechanisms of apoptosis. Intrinsic and extrinsic path of apoptosis. Involvement of mitochondria in apoptosis. The role of caspases. TNFR and Fas signaling pathways. Role of Bcl-2 family proteins.

Apoptosis: Molecular Mechanisms and Biological Role

Overview of Apoptosis

• Definition: Apoptosis is a form of programmed cell death that is essential for the development and maintenance of healthy tissues.
• Characteristics:
• Cell Shrinkage: Reduction in cell size.
• Chromatin Condensation: DNA condenses and fragments.
• Membrane Blebbing: Cell membrane forms bulges.
• Formation of Apoptotic Bodies: Cell breaks into smaller, membrane-bound fragments.
• Phagocytosis: Apoptotic bodies are engulfed and digested by phagocytes.

Biological Role of Apoptosis

Development:

• Embryogenesis: Removal of unnecessary cells during development.
• Tissue Homeostasis: Balances cell proliferation and death to maintain tissue integrity.

Immune System:

• Elimination of Infected Cells: Removal of cells infected by viruses or other pathogens.
• Self-Tolerance: Deletion of self-reactive immune cells to prevent autoimmunity.

Disease Prevention:

• Cancer Prevention: Elimination of damaged or potentially cancerous cells.

Molecular Mechanisms of Apoptosis

Pathways of Apoptosis

• Intrinsic Pathway (Mitochondrial Pathway):
• Trigger: Internal stress signals (e.g., DNA damage, oxidative stress).
• Key Players:
• Bcl-2 Family Proteins: Regulate mitochondrial outer membrane permeability.
• Cytochrome c: Released from mitochondria into the cytoplasm.
• Apaf-1: Binds cytochrome c and forms the apoptosome.
• Caspase-9: Activated by the apoptosome to initiate caspase cascade.
• Outcome: Activation of executioner caspases (e.g., caspase-3) leading to apoptosis.