Apoptosis Flashcards
Advantages to mass cell death
- Tissue homeostasis
- Tissue development
- Elimination of pathogen infected cells
- Remove injured cells
what are two ways cells die
gene independent (murder) or gene dependent (regulated cell death)
what are two gene-dependent classes of cell death
- Developmental/evolutionarily selected
2. Accidental (druggable)
2 general cell death morphologies
apoptosis, necrosis
3 molecularly defined pathways
apoptosis, necroptosis, and pyroptosis
how do caspases kill by apoptosis
have hundreds of protein substrates it chops up, caspase-3 activates other caspases and packages cell corpse for engulfment
Four steps in apoptotic death pathways
- Decision to die
- Execution : first pro-apoptotic gene is a protease Caspase 3
- Engulfment
- Degradation
BAX/BID role in cell death
Has BH3 motif that binds and inhibits BCL-2, leading to cell survival - tumor cells often “addicted” to BCL-2
Things to look for with apoptosis detection assays (4)
- Cytochrome C release
- Nuclear condensation
- phosphatidylserine (eat me signal) on cell surface
- Propidium iodide permeable, indicating “leaky” cell
How do cells die by necroptosis
RIPK dependent, stimulated by pathogens or tissue injury, phosphorylates MLKL which oligomerizes and leads to Rupture/Death
How do cells die by pyroptosis
Inflammasomes activated by pathogens or damage, form mega complex that activates Caspase-1, which then causes Gasermin D to oligomerize and rupture