Apoptosis Flashcards
Necrosis vs. Apoptosis
In necrosis, cell lyses and contents are spilled into extracellular space (effects groups of cells)
In apoptosis, contents are contained to the dying cell and cleaned up by phagocytic cells (effects individual cells)
Cell undergoing apoptosis shows
Morphological changes: blebbing bc of collapse of cytoskeleton Nuclear changes (pyknosis, loss of nuclear envelope) Cell surface changes: "eat me" signal
“eat me” signal is
phosphatidylserine (PS) expressed on outer surface for apoptotic cells
Two Major pathways of Apoptosis
Extrinsic Pathway: activation of cell-surface receptors (i.e. action of T-cell via antigens)
Intrinsic Pathway: response to cellular stress (i.e. DNA damage)
Caspases are synthesized as
Inactive proenzymes
Activated by cleavage of prodomains
Active caspases dimerize of heterodimerize for activity
Caspase cascade is…..
irreversible and highly amplified
Types of caspases
Initiator and Effector
Initiator requires scaffoliding (has CARD and DED domains)
Effector: does not require scaffolding and has prodomains cleaved by initiator
Extrinsic Pathway
external cell (i.e. T-lymphocyte) present FAS ligand to FAS receptor of cell to be killed
Bound receptor recruits adapter protein
Adapter protein binds procaspase 8
Aggregation of procaspases 8 get cleavage of prodomain and become active dimers leading to cascade.
Intrinsic Pathway
Cytochrome C gets released into cytoplasm from mitochondria
Cyt C binds to Apaf-1 in cytoplasm
Apaf1/ CytC complex binds procaspase 9
Prodomain of procaspase 9 gets cleaved and caspase 9 is activated.
Receptors of Extrinsic Pathway are _____ and activate _____
Death Receptors are activated by TNF-A, TRAIL and signal for FADD. FADD recruits procaspase 8/10
Apoptosome
The wheel of death
7 Apaf-1 bound to 7 Cytochrome C molecule
Recruits procaspase 9, by binding to Card Domain
Activates effector caspases 3,6,7
Smac/Diablo
Inhibit the inhibitors of apoptosis
Inhibitors of Apoptosis (IAP)
Inhibit effector caspases 3,6,7
Bcl-2 Family
Control Mitochondrial permeability in apoptosis
Bcl-2, Bcl-xL
BH4, BH3, BH1, BH2, TM
anti-apoptotic
