cell death review deck Flashcards
key feature of a cell undergoing autophagy
portions of cytoplasm engulfed by double membrane vacuole to for “autophagosome”, then becomes acificied to “autolysosome”
what are the 2 routes a cell in autophagy can go?
1- pro-survival- help a cell to survive in times of low nutrients
2- pro-death- cell progresses to apoptosis
how is autophagy used in normal cells? (2)
organelle turnover
supply amino acids through catabolism
in which diseases might one see cells undergoing autophagy?
cells with lots of improperly folded proteins (Huntington’s, prion dz, breast CA s/p tamoxifen)
what ultimately leads to apoptosis via then intrinsic pathway?
release of cytochrome C from mitochondria
what controls the release of cytochrome c from mitochondria?
bcl-2 family f proteins
- anti-apoptotic
- pro-apoptotic
- BH3-only
describe the anti-apoptotic proteins
Bcl-2 and Bcl-xL
in mito membrane
describe the pro-apoptotic proteins
Bax, Bak
dimerization indirectly results in release of cyto c from mito, levels will increase if cell is stressed
describe the BH3-only proteins (2 types)
activators- Bid/Bim- stimulate pore formation
decoys- Bad/Bik- inhibit the anti-apoptotic proteins
which initiator caspase is involved with intrinsic apoptosis?
caspase 9
steps of intrinsic apoptosis (5)
- cytochrome c released from mito
- cyto c binds with Apaf-1 adapter protein
- (Afap-1 + cyto C) bind procaspase 9 to form apoptosome
- procaspase 9 is activated to caspase 9
- caspase 9 triggers caspase cascade
what are the receptors for extrinsic apoptosis?
Fas receptor, tumor necrosis factor receptor
what are the ligands for extrinsic apoptosis?
Fas ligand, TNF-a (present on immune cells)
what is the initiator caspase for extrinsic apoptosis?
caspase 8
what are the actions of the caspase cascade? (4)
by effector caspases (caspase 3)
- in nucleus: cleave lamins, activate DFF, activate CAD, fragment nucleus
- cytoplasmic blebbing
- Ca2+ influx
- externalize phos-serine to signal to macrophages
what is extrinsic apoptosis an example of?
juxtacrine signaling
draw a picture of extrinsic apoptosis
:-)
what are the links between extrinsic and intrinsic apoptosis?
- both lead to activation of caspase 3
- caspase 8 can activate Bid (activator) at high enough concentrations, to activate intrinsic pathway
what will trigger anoikis?
when cell is detached from ECM
describe a “detached cell”
Bad binds to Bcl-2, thus inhibiting it, can cell process to apoptosis
describe “attached cell”
Bad is phosphorylated/inactivated by AtK kinase (via Pl-3 kinase), thus unable to inhibit Bcl-2 and apoptosis is avoided
what is the unfolded protein response?
triggered by misfiled proteins in RER, results in inhibition of protein synthesis, if it goes on long enough, can activate apoptosis via caspase 12
which diseases are related to UPR?
DM, neurodegenerative dz, viral infections
when does necrosis typically occur?
after toxic exposure or ischemia
