Lecture 25

Question 1

What is apoptosis?

Answer 1

Apoptosis is a distinctive and important mode of “programmed” cell death.

Question 2

What was the specimen studied I regards to apoptosis and who studied this?

Answer 2

They studied c. elegans - Robert Horvitz, Sydney Brenner and John E. Sulston
- They won a Nobel prize “for their discoveries concerning genetic regulation of organ development and programmed cell death”

Question 3

How do we see a dying cell?

Answer 3

We know the lineage of all cells in C. elegans
- We can therefore follow them in vivo
- They can see the cells dying.

Question 4

What mutant cells were isolated?

Answer 4

They isolated mutants in C. elegans that showed impaired
or failed clearance of apoptotic cells

Question 5

What is the apoptotic pathway?

Answer 5

3 stages:
1. specification
2. killing
3. execution.

Question 6

How do developing mice use apoptosis?

Answer 6

Sculpting the digits in the developing mouse paw by apoptosis. They go from webbed paws to individual digits.

Question 7

What is the use of apoptosis in connective tissue?

Answer 7

Apoptosis is required to clear the connecting tissue and
make arthropod joints.

Question 8

Difference between apoptotic cells and necrotic cells?

Answer 8

Necrotic cells spill their contents into their neighbors
- Apoptotic cells dies neatly, without damaging its neighbors.

Question 9

Cell membranes of apoptotic cells?

Answer 9

Apoptitic cells have intact plasma membranes.

Question 10

What molecule and pathway does apoptosis depend on?

Answer 10

Apoptosis depends on a proteolytic cascade mediated by Cysteine Aspartate Proteases = Caspases.

Question 11

What do caspases do when activated?

Answer 11

Once activated they cut strategic proteins in the cell.

Question 12

What is the action of caspases?

Answer 12

They are cysteine proteases that use the sulfur atom in cysteine to perform the cleavage reaction.
● they cut proteins next to
aspartate amino acids

Question 13

What is the role of initiator caspases? What are examples?

Answer 13

Initiator caspases begin the apoptotic program by activating the executioner caspases, which orchestrate the apoptosis program.
- Caspase 8 and 9 are initiators

Question 14

What is the role of effector caspases?

Answer 14

the executioner caspases orchestrate the apoptosis program
- Cascade 3,6,7 are effectors

Question 15

How are caspases synthesize an activated?

Answer 15

Caspases are synthesized as procaspases and are activated
by cleavage.
- Caspases are synthesized in the cell as inactive precursors, or procaspases,
- activated by cleavage at aspartic acids by other caspases

Question 16

What are imitator caspases?

Answer 16

Initiator caspases are inactive monomers that activate when
they dimerize and self cleave.

Question 17

What does an apoptotic signal trigger?

Answer 17

A apoptotic signal triggers the assembly of an adaptor-protein complex

Question 18

What activates executioner caspases?

Answer 18

Executioner caspases are cleaved and activated by
initiator caspases.
- executioner caspases have
shorter prodomains

Question 19

effect of caspase cascade?

Answer 19

Cascade of caspase activations make apoptosis amplifying
and irreversible
- caspases have specific targets

Question 20

What is a CAD, and what is its role?

Answer 20

A caspase activated DNAse (CAD) catalyzes the hydrolytic cleavage of
DNA

Question 21

Casepase release…?

Answer 21

Caspase release the brake on DNAses to degrade DNA.
Contained in dimer:
← Caspase-activated
deoxyribonuclease (DNAse).
← Regulatory subunits
← Caspase cleavage site

Question 22

What are the two main activated pathways of apoptosis?

Answer 22

Cells use two main activation pathways: one is signaled from outside the cell and is called the extrinsic pathway, and the other is signaled from
mitochondria inside the cell and is called the intrinsic pathway

Question 23

What initiates the extrinsic pathway?

Answer 23

Activation of cell-surface death receptors initiates the extrinsic pathway

Question 24

effect of activated Fas receptors?

Answer 24

activated Fas receptors cluster and expose death domains on the receptor tails, which then bind and cluster a small intracellular adaptor protein called FADD

Question 25

Wha't does FADD clusters form?

Answer 25

FADD clusters recruit multiple copies of inactive initiator caspases, which oligomerize. The large structure is called the death-inducing signaling complex (DISC)

Question 26

When is intrinsic signalling used?

Answer 26

Cells can also activate their apoptosis program from inside the cell, often in response to developmental signals or to injury such as DNA damage.

Question 27

What signal activates intrinsic pathway? `

Answer 27

The release of cytochrome c from the mitochondria into the cytoplasm is the signal that activates the intrinsic pathway activation

Question 28

What does binding of cytC to Apaf1 cause?

Answer 28

The binding of cytochrome c to Apaf1 exposes an oligomerization domain and a caspase recruitment domain

Question 29

ROle of Apaf1?

Answer 29

The oligomerized Apaf1 recruits an inactive caspase-9 monomer, forming the apoptosome. Then, the caspase-9 monomers are activated by dimerization.

Question 30

What does Apaf1 activate?

Answer 30

Apaf1 activates caspases by oligomerizing into a huge complex called the apoptosome ● Apaf1 = apoptotic protease activating factor 1

Question 31

What is a line of defence against inappropriate asps activation?

Answer 31

Another line of defense against inappropriate caspase activation is provided by caspase inhibitor proteins called inhibitors of apoptosis (IAPs). ● IAPs bind and prevent activation of some procaspases

Question 32

What proteins mainly regulate the intrinsic pathway?

Answer 32

Bcl2 proteins are the main regulators of the Intrinsic Pathway

Question 33

Role of pro and anti apoptotic proteins?

Answer 33

- Pro-apoptotic Bcl2 proteins make holes into the mitochondrial membrane - Anti-apoptotic Bcl2 proteins inactivate the pro-apoptotic Bcl2

Question 34

healthy neighbours apoptosis?

Answer 34

Healthy Neighbors Phagocytose and Digest Apoptotic Cells ● Cell competition is a fitness control mechanism in which less fit cells are eliminated from a tissue

Question 35

Flippase degradation caspases?

Answer 35

Caspases degrade a flippase that keeps Phosphatidyl serine inside the cell - In apoptotic cells PtdSer is outside - Normal cells recognize apoptotic cells because they have PtdSer outside

Question 36

What is ferroptosis? 1

Answer 36

Ferroptosis is an intracellular iron-dependent form of cell death that is distinct from apoptosis and necrosis

Question 37

What is characteristic of ferroptosi?

Answer 37

Ferroptosis is characterized by the accumulation of oxidatively damaged phospholipids (lipid peroxidation).