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Purposes Of Apoptosis

Purposes Of Apoptosis. Eliminate cells not needed by organism. During development: sculpting, remove excess neurons Adult. Maintain tissue size Eliminate autoreactive immune cells, DNA damaged cells. Morphological Changes. Distinct from necrosis: injured cell bursts, inflammatory response

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Purposes Of Apoptosis

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  1. Purposes Of Apoptosis Eliminate cells not needed by organism • During development: sculpting, remove excess neurons • Adult • Maintain tissue size • Eliminate autoreactive immune cells, DNA damaged cells

  2. Morphological Changes • Distinct from necrosis: injured cell bursts, inflammatory response • Apoptosis: orderly intracellular changes, dying cell phagocytosed

  3. Caspases • Protease with cysteine at active sites • Cleave substrates at specific aspartic acids • Synthesized as procaspases and activated by other caspases

  4. Caspase Cascade • Amplifying cascade involving initiator and executioner caspases • Executioner caspases cleave substrates responsible for cell death

  5. Induction Of Caspase Cascade • Adaptor proteins aggregate initiator procaspases • Mutual cleavage of weakly active procaspases • Different adaptors activated by intracellular or extracellular stimuli

  6. Extrinsic Pathway • Ligand induces aggregation of death receptors on cell surface • Death receptors recruit adaptor proteins that bind and aggregate initiator procaspases

  7. Intrinsic Pathway • Mitochondria induced to release cytochrome c • Cytochrome c causes aggregation of Apaf-1 adaptor proteins that aggregate initiator procaspases

  8. Bcl2 Family • Regulators of intrinsic pathway • Pro- and anti-apoptotic types affect cytochrome c release • Bind and inhibit each other’s activities • Balance determines cells live or die

  9. BH123 Pro-Apoptotic Proteins • Stimulate release of cytochrome c • Required for intrinsic pathway

  10. Anti-Apoptotic Bcl2 Family • Bind to and inhibit pro-apoptotic • Required for cell survival • Inhibited during intrinsic pathway

  11. BH3-Only Pro-Apoptotic Proteins • Bind to and inhibit anti-apoptotic • Activated by apoptotic stimuli (deprivation of survival factors, p53 response to DNA damage)

  12. Survival Factors • Cells deprived of survival factors activate intracellular death program • Competition for survival factors can regulate cell number

  13. Mechanism Of Survival Factors • Signaling through Bcl2 family • Transcriptional activation of anti-apoptotic Bcl2 proteins • Akt kinase inactivates BH3-only pro-apoptotic protein, allowing Bcl2 to suppress apoptosis

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