1. Apoptosis is a tightly regulated form of programmed cell death that plays an important role in development, tissue homeostasis, and the immune system. It is characterized by morphological changes including cell shrinkage, chromatin condensation, and formation of apoptotic bodies. 2. The process of apoptosis involves initiator caspases that activate executioner caspases, leading to degradation of nuclear and cytoplasmic components. Mitochondria also play a key role by releasing pro-apoptotic factors. Various proteins regulate apoptosis, including Bcl-2 family members and inhibitors of apoptosis (IAPs). 3. Dysregulation of apoptosis contributes to diseases like cancer, neurodegeneration, and HIV/AIDS. Detection of

4. Physiologic or pathologic Invariably pathologic Physiologic or pathologic Intact released into apoptotic bodies Enzymatic digestion,leak out Cellular contents no frequent Adjacent inflammation Intact,altered structure disrupted Plasma membrane Fragmentation into nuleosome fragments pkynosis ,karyorhexis,karyolysis Nucleus Reduced (shrinkage) Enlarged swelling) Cell size Apoptosis Necrosis Features

13. APOPTOSIS: important in embryogenesis Morphogenesis (eliminates excess cells): Selection (eliminates non-functional cells):

14. APOPTOSIS: important in embryogenesis Immunity (eliminates dangerous cells): Self antigen recognizing cell Organ size (eliminates excess cells):

15. APOPTOSIS: important in adults Tissue remodeling (eliminates cells no longer needed): Virgin mammary gland Late pregnancy, lactation Involution (non-pregnant, non-lactating) Apoptosis Apoptosis - Testosterone Prostate gland

16. APOPTOSIS: important in adults Tissue remodeling (eliminates cells no longer needed): Resting lymphocytes + antigen (e.g. infection) - antigen (e.g. recovery) Apoptosis Steroids, immunosuppressants: kill lymphocytes by apoptosis Lymphocytes poised to die by triggering apoptosis

17. APOPTOSIS: important in adults Maintains organ size and function : Apoptosis + cell division Cells lost by apoptosis are replaced by cell division

20. STAGES OF APOPTOSIS Healthy cell DEATH SIGNAL Commitment to die (reversible) EXECUTION (irreversible) Dead cell (condensed, crosslinked) ENGULFMENT DEGRADATION

21. STAGES OF APOPTOSIS Genetically controlled: Caenorhabditis elegans Soil nematode (worm) Healthy cell Dead cell Committed cell ces2 ces1 ced9 ced3,4 BCL2 Caspases C. Elegans genes == mammalian genes

31. CASPASE ACTIVATION MECHANISMS

37. APOPTOSIS: control Receptor pathway (physiological): Death receptors: (FAS, TNF-R, etc) FAS ligand TNF Death domains Adaptor proteins Pro-caspase 8 (inactive) Caspase 8 (active) Pro-execution caspase (inactive) Execution caspase (active) Death MITOCHONDRIA

49. Cells are balanced between life and death DAMAGE Physiological death signals DEATH SIGNAL PROAPOPTOTIC PROTEINS ANTIAPOPTOTIC PROTEINS

51. APOPTOSIS: control Intrinsic pathway (damage): Mitochondria Cytochrome c release Pro-caspase 9 cleavage Pro-execution caspase (3) cleavage Caspase (3) cleavage of cellular proteins, Nuclease activation, Etc. Death BAX BAK BOK BCL-Xs BAD BID B IK BIM NIP3 BNIP3 BCL-2 BCL-XL BCL-W MCL1 BFL1 DIVA NR-13 Several viral proteins Pro apoptotic Anti apoptotic

57. Cross talk between apoptotic pathways

70. APOPTOSIS: Role in Disease Neurodegeneration PARKINSON'S DISEASE ALZHEIMER'S DISEASE HUNTINGTON'S DISEASE STROKE

76. APOPTOSIS: Role in Disease Cancer Apoptosis eliminates damaged cells (damage => mutations => cancer Tumor suppressor p53 controls senescence and apoptosis responses to damage Most cancer cells defective in apoptotic response High levels of anti-apoptotic proteins or Low levels of pro-apoptotic proteins ===> CANCER

77. APOPTOSIS AND HIV

82. Thank you!