Cell death

• Necrosis


  Uncontrolled cell death, associated with disease
• Apoptosis


  Programmed cell death or cell suicide, essential for normal health and development
• Types of cell death

  • Apoptotic cell
  • Necrotic cell
• Importance of apoptosis


  • Embryo development
  • Immune system
  • Homeostasis
  • Cancer
• Embryo development


  Sculpting tissue
• Immune system


  Destroying self-reacting immune cells<|>Destroying virus infected cells
• Homeostasis


  Counter-balance to cell division and removal of old or damaged cells
• Cancer


  Radiotherapy and most chemotherapy drugs work by inducing apoptosis
• Many cancer cells have defects in the apoptosis pathways that make them resistant to apoptosis
• Two main pathways for triggering apoptosis

  • Receptor mediated (extrinsic pathway)
  • Mitochondria mediated (intrinsic pathway)
• Intrinsic pathway


  Can be activated via the mitochondria by a variety of cell stresses such as free radical damage, DNA damage, viral infection, or loss of survival signals
• Types of apoptotic caspases

  • Initiator caspases
  • Effector (executioner) caspases
• Initiator caspases


  Activate other caspases
• Effector caspases


  Break down cellular components such as the cytoskeleton and DNA
• Caspases are the chief executioners of apoptosis
• Cytochrome C


  Located in the inner mitochondrial membrane and is an essential component of the electron transport chain
• To trigger apoptosis, pores form in the outer mitochondrial membrane allowing release of cytochrome C into the cytosol
• Apoptosome


  Multi-protein complex formed when cytochrome C binds to other cytosolic proteins
• Formation of the apoptosome requires

  • Cytochrome C
  • Apaf-1
  • Pro-caspase 9
  • ATP
• Bcl-2 proteins


  Regulate the release of cytochrome C from the mitochondria
• Members of the Bcl-2 family


  • Pro-apoptotic members
  • Anti-apoptotic members
• Pro-apoptotic members


  Promote the formation of large pores in the outer membrane that leads to the release of cytochrome C
• Anti-apoptotic members


  Block the action of the pro-apoptotic members
• Programmed cell death (apoptosis) is essential for normal health and development
• The mitochondria play a central role in the regulation of apoptosis and can be regarded as one of the main checkpoints in the process
• Bcl-2 proteins act on the mitochondria to regulate the formation of pores in the outer mitochondrial membrane
• The result of Bcl-2 protein action depends on the balance between pro-apoptotic and anti-apoptotic Bcl-2 proteins
• Release of cytochrome C from the inner mitochondrial membrane to the cytosol leads to the formation of the apoptosome and activation of the caspase cascade
• The caspases are responsible for the destruction of the cell