Lecture Notes: Apoptosis - Programmed Cell Death

Introduction

• Apoptosis is the process of programmed cell death.
• Essential in eliminating faulty cells that threaten an organism's survival.
• Mutations in genes regulating apoptosis can cause cancer.
  • Failure to undergo apoptosis leads to uncontrollable cell proliferation, forming tumors.

Apoptosis Process

• Mechanism:
  • Cellular agents fragment all cell components: DNA, organelles.
  • Cell shrinks into lobes, digested by scavenger cells.
  • Prevents potential incorporation of faulty components into other cells.

Initiation of Apoptosis

• Extrinsic Pathway:

  • Signals from outside the cell.
  • Nearby cells release signaling molecules initiating apoptosis.

• Intrinsic Pathway:

  • Signals from inside the cell.
  • Triggered by irreparable DNA damage through protein-protein interactions.

Case Study: C. elegans

• C. elegans:

  • Small nematode used in research due to its simple cell structure.
  • Apoptosis occurs at specific developmental times.

• Key Genes Involved:

  • ced-3 and ced-4: Encode proteins for apoptosis.
  • Ced-9: Encodes a protein that inhibits apoptosis, located in the outer mitochondrial membrane.
  • Signal transduction alters Ced-9, leading to apoptosis through proteases and nucleases like capsases.

Apoptosis in Humans

• More complex than in C. elegans with multiple capsases and pathways.

• Mitochondrial proteins may form pores to aid signal transduction for apoptosis.

• Triggers:

  • External signals can trigger mitochondrial response.
  • Internal signals from the nucleus or endoplasmic reticulum if damage/misfolding occurs.

Role in Development

• Developmental Significance:
  • Necessary for limb formation, nervous system development.
  • Found in most eukaryotic life, indicating early evolutionary development.

Clinical Implications

• Degenerative Diseases:

  • Issues with apoptosis linked to diseases like Alzheimer’s and Parkinson’s.
  • Protein aggregation can trigger apoptosis, leading to neuron death.

• Oncogenesis:

  • Failed apoptosis due to genetic mutations can lead to cancer.

Conclusion

• Apoptosis is crucial for eliminating dangerous cells, normal development, and preventing cancer.
• Understanding its mechanism is vital for comprehending various diseases and developmental biology.