Lecture 25 - Cell Death

Question 1

why do cells undergo apoptosis?

Answer 1

• embryonic development requires the elimination of excess cells
• cells that sustain irreparable genomic damage need to be removed
• removal of cells that aren’t useful anymore

Question 2

failure to carry out apoptosis leads to…

Answer 2

cancer

Question 3

overzealous apoptosis leads to…

Answer 3

diabetes

Question 4

what characterizes apoptosis?

Answer 4

1. overall shrinkage in volume of the cell and nucleus
2. loss of adhesion to neighbouring cells
3. formation of blebs on the cell surface
4. fragmentation of the genome

Question 5

what engulfed cell corpses through phagocytosis?

Answer 5

neutrophils or macrophages

Question 6

def: less orderly form of cell death

Answer 6

necroptosis

Question 7

what characterizes necroptosis?

Answer 7

• swelling of the cell and internal organelles
• membrane breakdown
• leakage of the cell contents into the extracellular space
• the induction of inflammation

Question 8

why does necropolis usually happen?

Answer 8

when cells fail to undergo apoptosis following exposure to stressors

Question 9

how can necroptosis be beneficial?

Answer 9

can lead to an inflammation response

Question 10

apoptosis is like __________ ______________
necroptosis is like __________ _____________

Answer 10

controlled implosion
uncontrolled explosion

Question 11

def: group of cysteine proteases that are responsible for triggering most of the changes during cell death

Answer 11

caspases

Question 12

what do caspases cleave?

Answer 12

• cytoskeletal compnents, disrupting cell shape
• lamins, breaking down nucleus
• protein kinases, regulate cell adhesion
• DNase inhibitors, activate DNases that fragment genome

Question 13

what is induction of the apoptotic triggered by?

Answer 13

1. external (extrinsic pathway)
2. internal (intrinsic pathway)

Question 14

what is the death receptor on the extracellular side of the cell?

Answer 14

trimeric transmembrane TNF receptor protein

Question 15

what does receptor ligand binding induce in the TNF receptor, in extrinsic apoptosis?

Answer 15

induces conformational change of the TNF receptor, leading to the recruitment of cytosolic proteins

Question 16

what leads to trans-autocleavage within the cell?

Answer 16

clustering of procaspases upon recruitment to membrane-bound (early) and cytosolic (late) complexes

Question 17

how does procaspase-8 become active/inactive?

Answer 17

inactive with pro region
active without pro region

Question 18

cascade-8 is an ___________ caspase that activates _________ caspases, which carry out the destruct of the cell

Answer 18

initiator, executioner

Question 19

what do internal signals for intrinsic cell death activate within the cells?

Answer 19

the Bcl-2 family of proteins, which can target Bax to the mitochondrial membrane

Question 20

what happens to Bax when it is target to the mitochondrial membrane?

Answer 20

undergoes a conformational change, which allows it to form a multi-subunit membrane channel in the outer mitochondrial membrane

Question 21

what resides in the inter membrane space and is released into the cytosol upon Bax forming a channel in the outer mitochondrial membrane?

Answer 21

cytochrome c

Question 22

what does cytochrome C do ?

Answer 22

forms a wheel-shaped complex, called an apoptosome, which brings together procaspase-9

Question 23

T or F: initiation of procaspase-9 does not require proteolytic cleavage, activated simply by joining the apoptosome

Answer 23

true

Question 24

in necroptosis, what is not activated?

Answer 24

caspase-8

Question 25

what happens in the necrosome?

Answer 25

series of interactions result in oligomerization an activation of RIP1K and RIP3K

Question 26

what does kinase RIP3K activate?

Answer 26

MLKL which gets targeted to the plasma membrane after it is phosphorylated

Question 27

what does MLKL do?

Answer 27

scrambles the phospholipids, causing the membrane to lose integrity and the cell dies