cell death review deck

Question 1

key feature of a cell undergoing autophagy

Answer 1

portions of cytoplasm engulfed by double membrane vacuole to for “autophagosome”, then becomes acificied to “autolysosome”

Question 2

what are the 2 routes a cell in autophagy can go?

Answer 2

1- pro-survival- help a cell to survive in times of low nutrients
2- pro-death- cell progresses to apoptosis

Question 3

how is autophagy used in normal cells? (2)

Answer 3

organelle turnover

supply amino acids through catabolism

Question 4

in which diseases might one see cells undergoing autophagy?

Answer 4

cells with lots of improperly folded proteins (Huntington’s, prion dz, breast CA s/p tamoxifen)

Question 5

what ultimately leads to apoptosis via then intrinsic pathway?

Answer 5

release of cytochrome C from mitochondria

Question 6

what controls the release of cytochrome c from mitochondria?

Answer 6

bcl-2 family f proteins

• anti-apoptotic
• pro-apoptotic
• BH3-only

Question 7

describe the anti-apoptotic proteins

Answer 7

Bcl-2 and Bcl-xL

in mito membrane

Question 8

describe the pro-apoptotic proteins

Answer 8

Bax, Bak

dimerization indirectly results in release of cyto c from mito, levels will increase if cell is stressed

Question 9

describe the BH3-only proteins (2 types)

Answer 9

activators- Bid/Bim- stimulate pore formation

decoys- Bad/Bik- inhibit the anti-apoptotic proteins

Question 10

which initiator caspase is involved with intrinsic apoptosis?

Answer 10

caspase 9

Question 11

steps of intrinsic apoptosis (5)

Answer 11

• 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

Question 12

what are the receptors for extrinsic apoptosis?

Answer 12

Fas receptor, tumor necrosis factor receptor

Question 13

what are the ligands for extrinsic apoptosis?

Answer 13

Fas ligand, TNF-a (present on immune cells)

Question 14

what is the initiator caspase for extrinsic apoptosis?

Answer 14

caspase 8

Question 15

what are the actions of the caspase cascade? (4)

Answer 15

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

Question 16

what is extrinsic apoptosis an example of?

Answer 16

juxtacrine signaling

Question 17

draw a picture of extrinsic apoptosis

Answer 17

:-)

Question 18

what are the links between extrinsic and intrinsic apoptosis?

Answer 18

• both lead to activation of caspase 3

- caspase 8 can activate Bid (activator) at high enough concentrations, to activate intrinsic pathway

Question 19

what will trigger anoikis?

Answer 19

when cell is detached from ECM

Question 20

describe a “detached cell”

Answer 20

Bad binds to Bcl-2, thus inhibiting it, can cell process to apoptosis

Question 21

describe “attached cell”

Answer 21

Bad is phosphorylated/inactivated by AtK kinase (via Pl-3 kinase), thus unable to inhibit Bcl-2 and apoptosis is avoided

Question 22

what is the unfolded protein response?

Answer 22

triggered by misfiled proteins in RER, results in inhibition of protein synthesis, if it goes on long enough, can activate apoptosis via caspase 12

Question 23

which diseases are related to UPR?

Answer 23

DM, neurodegenerative dz, viral infections

Question 24

when does necrosis typically occur?

Answer 24

after toxic exposure or ischemia

Question 25

what is the distinguishing factor about necrosis?

Answer 25

involves breakdown of cell membrane integrity and inflammatory response

Question 26

which types of cell death have cross talk between them?

Answer 26

autophagy & apoptosis

Question 27

what can lead to the degradation of caspase 8 and inhibition of apoptosis?

Answer 27

beclin + other Atg proteins needed to form autophagosome

Question 28

what is the effect of caspase on beclin/Atg proteins?

Answer 28

caspases can cleave beclin/Atg and inhibit autophagosomy

Question 29

what is necroptosis? what proteins does it use?

Answer 29

programmed necrosis, uses RIP1 and RIP3 - does NOT use caspases

Question 30

entosis

Answer 30

cellular cannibalism seen in tumors

Question 31

parthanatos

Answer 31

poly-ADP-ribose polymerase-1 = enzyme that causes cell death pathway