Cell Death Chapter 23

Study Notes

Passive, pathological process
Induced by cellular injury or accidental means
Often involves the simultaneous death of groups of cells
Necrotic cells have ruptured cell membranes, causing cytoplasm and organelles to spill into surrounding tissue fluids
Often induces an inflammatory response

Active, normal, physiological process
Removes individual cells without damaging neighboring cells or inducing inflammation
Cells have a characteristic "blebbed" appearance of their membranes
Fundamental to cellular and tissue physiology, akin to cell division and differentiation
Disturbances in apoptosis pathways may lead to cancers, autoimmune diseases, and neurodegenerative disorders

Cell shrinkage, but not lysis
Plasma membrane remains intact, but portions bud off (blebbing)
Phosphatidylserine in the inner membrane flips to the cell surface, serving as an "eat-me" signal to phagocytic cells
Mitochondria releases cytochrome c in an ATP-dependent process, but remains within blebs
Chromatin segments and condenses

Removal of damaged cells
Removes cells damaged beyond repair, infected, or starved, saving nutrition and preventing viral spread
p53 protein halts cell cycle and stimulates apoptosis
During development, apoptosis removes excess cells for normal development and function
Selective apoptosis "sculpts" the developing tissues
Incomplete apoptosis can result in abnormal structures

Apoptosome (Internal Cell Death Program)
- Initiated by irreparable damage to cellular components or DNA
- Bax (proapoptotic protein) is inserted into the mitochondrial membrane, allowing cytochrome c to exit into the cytoplasm
- Cytochrome c in the cytosol triggers the formation of Apoptosome using ATP
- Cytoplasmic cytochrome c activates the apoptotic protease activating factor (Apaf-1) adaptor protein, which activates caspase 9
Death receptor (External Cell Death Program)
- Triggered by death receptors (e.g., Fas, TNFR)
- Recognizes specific ligands, such as TNFR and Fas ligand
- Adaptor molecules (e.g., FADD, TRADD) interact with death receptors to transmit the apoptotic signal to the death machinery

Stimulated to degrade cellular components in the apoptotic cell
Proteases that are major effectors of apoptotic cell death
Members of the cysteine protease class
Synthesized as inactive zymogen or proenzyme forms and are activated to become functional proteases when needed