Apoptosis

Question 1

What is the overall process of apoptosis

Answer 1

Overall process of apoptosis(after activation by caspases)
1. Cell shrinks
2. Blebs form
3. Chromatin condenses
4. Cytoskeleton collapses and nuclear envelope disintegrates
5. Apoptotic bodies form (vesicles are released by the dying cell as it packages its contents into vesicles which are engulfed by a macrophage)
6. Cell is phagocytosed (the vesicles re marked with phosphotidylserine and the macrophage breaks down the contents of the vesicle)

Question 2

What are the two types of cell death

Answer 2

Apoptosis
Necrosis

Question 3

What is necrosis

Answer 3

Cell swells and bursts and releases its content into the environment
It therefore exposes other cells to what caused its death which can cause death for other cells
Occurs for cells that die in response to a trauma or lack of blood supply, they swell and burst

Question 4

What is the difference between apoptosis and necrosis

Answer 4

Necrosis is quick whereas apoptosis is slower
Apoptosis is a clean death

Question 5

Why is apoptosis needed

Answer 5

apoptosis needed for maintenance of tissue size- requires cells to die at the same rate as they are produced

Question 6

What did sulston and brenner do

Answer 6

Question 7

What are caspases

Answer 7

Caspases are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cysteine protease activity – a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue

They are crucial for the controlled dismantling of cellular components during apoptosis and for activating inflammatory processes

Question 8

How are caspases activated (intrinsic pathway )

Answer 8

Mitochondrial Permeabilization:

Stress signals cause the permeabilization of the mitochondrial outer membrane.
Cytochrome c is released from the mitochondria into the cytosol.
Apoptosome Formation:

Cytochrome c in the cytosol binds to Apaf-1 (apoptotic protease activating factor-1).
This complex recruits and binds to procaspase-9, forming a structure known as the apoptosome.
Activation of Caspase-9:

The apoptosome facilitates the dimerization and activation of procaspase-9.
Active caspase-9 then cleaves and activates effector caspases, such as caspase-3, caspase-6, and caspase-7.

Question 9

What are initiators

Answer 9

Initiator caspases begin the apoptotic process and activate executioners

Question 10

What are executioners

Answer 10

Executioner caspases catalyse the widespread protein cleavage events that kill the cell

Question 11

What is an adaptor protein

Answer 11

It acts as a bridge between a caspases and a pro apoptosis signal

Question 12

What is an example of a regulator of apoptosis and what are the two types

Answer 12

Bcl-2
The two types:
- pro apoptotic- promote cell death
- anti apoptotic- prevent cell death

• Some Bcl2 = pro apoptotic, some are anti-apoptotic
• Antiapoptotic proteins inhibit apoptosis by blocking the release of cytochrome c
• Proapoptotic proteins promote apoptosis by promoting the release of cytochrome c

Question 13

What are the two pathways in which apoptosis can be triggered

Answer 13

The intrinsic pathway which comes from within the cell
The extrinsic pathway which occurs due to an extra cellular signal

Question 14

What decides whether a cell lives or dies

Answer 14

apoptosis can be activated from within In response to e.g DNA damage

• Pro-apoptotic and anti-apoptotic proteins bind to eachother and inhibits eachothers function
• The balance between pro and anti apoptotic proteins determines whether a cell dies of lives

Question 15

Describe the process of the extrinsic pathway and how its activated

Answer 15

• extracellular signals bind to cell surface death receptors which triggers extrinsic pathway of apoptosis
• These death receptors are transmembrane proteins
Activation
• Fas ligands on the surface of a killer lymphocyte interacts with Fas receptor on cell surface
• This leads to clustering of several ligand-bound receptors
• The receptor clustering activates death domains on the receptor tails
• The receptor tails interact with the FADD domain on the adaptor protein
• Each FADD recruits an initiator caspase which forms a death inducing signalling complex (DISC)
• Within the DISC two adjacent initiators interact and cleave one another to form an activated protease dimer
• This dimer cleaves itself in the area where its linked to the death effector domain
• The active caspase dimer is released into the cytosol where it activated executioners

(Then rest of apoptosis process)

Question 16

How are caspases activated

Answer 16

• initiator Caspase contains a protease domain and a small protein interaction domain
• Apoptosis signals trigger the assembly of adaptor proteins which carry multiple binding sites for the Caspases’ small protein interaction domain
• initiator caspases bind to adaptor proteins - caspases activate And a specific site in the caspases protease domain is cleaved
• Each protease domain of the caspase is rearranged into a small and large subunit
• executioner caspases are activated by initiator caspases - when the initiator Caspase cleaves a site in the protein domain of the executioner, it undergoes a conformational change
• The executioner then cleaves a variety of proteins
• (One initiator complexcan activate many executioners - triggers a cascade

Question 17

How is apoptosis truggered

Answer 17

• apoptosis is triggered by caspases which cleave the target proteins at specific aspartic acids
• Caspases have cysteine at their active site
• caspases are synthesised as inactive precursors- they’re only activated during apoptosis
• Two major classes of apoptosis caspases- initiator and executioner caspases

Question 18

What is meant by the domain of a protein

Answer 18

subunit which has a specific role (subunit = polypeptide)

Question 19

What is the role of Bcl-2

Answer 19

It stops pore formation (which stops cytochrome being released into the cytoplasm)and therefore stops apoptosis

Question 20

What is the role of Bak and Bax

Answer 20

If DNA of a cell is damaged lots of Bak and Bax is produced
They pierce the mitochondrial outer membrane (Form a pore)
Allows cytochrome to exit into the nucleus for apoptosis to occur via the intrinsic pathway

Question 21

Describe the process of the intrinsic pathway

Answer 21

Intrinsic pathway - apoptosis can be activated from within In response to e.g DNA damage
Process :
- Bak and Bax rebates pore in mitochondrial membrane- cytochrome c is released
- cytochrome x combined with Apaf-1 and procaspase 9 to produce an Apoptosome which triggers caspase 9
- caspase- signalling caspase cascade activated
- then the rest of apoptosis occurs (phagocytosis etc)