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• 1 Molecular and Biological Aspects of Apoptosis

• 1.1 Types of cell death

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• Autophagic cell death

  Dying cells displaying a large-scale accumulation of autophagosomes. Is considered as a pro-survival pathway in the dying cell.

• 4 functions of programmed cell death

  1. Sculpting
     
  2. Deleting unwanted structures
  3. Controlling cell numbers
  4. Eliminating nonfunctional, harmful, abnormal, or misplaced cells
     

• 1.2 Introduction

• What are the different routes in the death pathway?

  1. Apoptosis (red): via caspase-9 activation and a mitochondrial route or directly via caspase-8 to caspase-3 as a primary effector caspase.
     
  2. Autophagic (pink): apoptosis-like
  3. Necrotic (black): osmotic rupture, or depletion of energy in the apoptotic route.
  4. Other (green)

• Necrosis: morphological features

  • Loss of membrane integrity
    
  • Flocculation of chromatin
  • Swelling of the cell and lysis
  • No vesicle formation, complete lysis
  • Disintegration (swelling) of organelles

• Apoptosis: morphological features

  • Membrane blebbing, but no loss of integrity
    
  • Aggregation of chromatin at the nuclear membrane
  • Cellular condensation (cell shrinkage)
  • Formation of membrane-bound vesicles (apoptotic bodies)
  • No disintegration of organelles; organelles remain intact

• Necrosis: biochemical features

  • Loss of regulation of ion homeostasis
    
  • No energy requirement (passive process, also at 4 degrees)
  • Random digestion of DNA (smear of DNA on gel)
  • Postlytic DNA fragmentation (late event)

• Apoptosis: biochemical features

  • A tightly regulated process involving activation and enzymatic steps
    
  • Energy (ATP)-dependent (active process, not at 4 degrees)
  • Non-random mono- and oligonucleosomal length fragmentation of DNA (ladder pattern on gel)
  • Prelytic DNA fragmentation (early event)

• Necrosis: physiological significance

  • Death of cell groups
    
  • Evoked by non-physiological disturbances
  • Phagocytosis by macrophages
  • Significant inflammatory response

• Apoptosis: physiological significance

  • Death of single, individual cell
    
  • Induced by physiological stimuli
  • Phagocytosis by adjacent cells or macrophages
  • No inflammatory response

• Three phases of apoptosis

  1. Activation phase (death receptor signaling): via extrinsic or intrinsic pathway
  2. Execution phase (mitochondrial signaling)
  3. Burial phase (caspase cascade)