APOPTOSIS

What event commits intrinsic apoptosis?

Cytochrome c release from mitochondria

What event commits extrinsic apoptosis?

DISC-mediated activation of caspase-8

What destroys the cell?

Executioner caspases dismantle essential proteins

What defines apoptosis?

Programmed

What happens when apoptosis is too low?

Cancer and autoimmune disease (cells refuse to die)

What happens when apoptosis is too high?

Neurodegeneration or tissue atrophy

How do tumours block apoptosis?

Overexpress Bcl-2 family proteins or mutate p53

Why are Bcl-2 proteins drug targets?

Blocking them reinstates apoptosis in tumour cells

Name a Bcl-2 inhibitor

Venetoclax

How do viruses interfere with apoptosis?

Encode Bcl-2 mimics or caspase inhibitors to avoid immune clearance

How are apoptotic cells removed?

Phagocytes recognise “eat-me” signals like phosphatidylserine exposure

Why is clearance important?

Prevents inflammation and autoimmunity

What happens if apoptotic cells are not cleared?

Secondary necrosis and immune activation

How do extrinsic and intrinsic pathways converge?

At caspase-3 activation

How does extrinsic link to intrinsic?

Caspase-8 cleaves Bid into tBid → activates Bax/Bak

Why is cross talk important?

Allows amplification and failsafe activation

Which checkpoint protein can induce apoptosis?

p53

How does p53 promote apoptosis?

Upregulates pro-apoptotic genes (Puma

What does IAP stand for?

Inhibitor of apoptosis protein

What do IAPs do?

Bind and inhibit active caspases

Why do cells need IAPs?

Prevent accidental caspase activation

How are IAPs neutralised?

Mitochondrial proteins like Smac/DIABLO bind and block IAPs

What does Smac release accomplish?

Allows caspases to fully activate and execute death

What is the role of Bcl-2 family?

Control mitochondrial membrane permeabilisation

Name two anti-apoptotic Bcl-2 proteins

Bcl-2 and Bcl-XL

Name two pro-apoptotic effectors

Bax and Bak

What activates Bax/Bak?

BH3-only proteins sensing stress signals

Name BH3-only proteins

Bid

What do Bax/Bak do?

Form pores allowing cytochrome c release

How do Bcl-2 proteins inhibit apoptosis?

Bind Bax/Bak and prevent pore formation

What determines apoptosis threshold?

Balance of pro- vs anti-apoptotic Bcl-2 proteins

What triggers intrinsic apoptosis?

Stress inside the cell e.g. DNA damage

Which organelle governs the intrinsic pathway?

Mitochondria

What happens at mitochondria during apoptosis?

Outer membrane permeabilisation

What does mitochondrial permeabilisation release?

Cytochrome c

Where does cytochrome c go?

Cytosol

What complex does cytochrome c form?

Apoptosome

What protein assembles apoptosome?

Apaf-1

Which initiator caspase does apoptosome activate?

Caspase-9

Why is cytochrome c release irreversible?

Commitment to executioner caspase activation

What triggers extrinsic apoptosis?

Binding of extracellular death ligands

Name two death ligands

FasL and TNF-α

What does FasL bind?

Fas (CD95) receptor

What complex forms at Fas?

Death-inducing signalling complex (DISC)

Which adaptor assembles DISC?

FADD (Fas-associated death domain)

Which initiator caspase is recruited to DISC?

Caspase-8

What does active caspase-8 do?

Directly activates executioner caspases or cleaves Bid to link to mitochondrial pathway

Why is extrinsic pathway rapid?

Direct receptor signalling pulls procaspases into clusters for activation

What are caspases?

Cysteine proteases that cleave proteins to dismantle the cell

What does “caspase” stand for?

Cysteine-aspartate protease

How are caspases produced?

As inactive zymogens (procaspases)

What activates caspases?

Proteolytic cleavage during apoptotic signalling

Name two initiator caspases

Caspase-8 and caspase-9 (either acceptable)

Name two executioner caspases

Caspase-3

What do executioner caspases do?

Cleave structural and regulatory proteins to dismantle the cell

Which proteins are caspase targets?

Cytoskeleton

Why must caspases be tightly controlled?

Accidental activation can kill healthy cells

What is apoptosis?

Programmed cell death controlled by signalling pathways

Why is apoptosis essential?

Removes damaged

How does apoptosis differ from necrosis?

Apoptosis is controlled and tidy; necrosis is uncontrolled and inflammatory

Name two triggers of apoptosis

Developmental cues

What hallmarks define apoptosis?

Cell shrinkage

What happens to apoptotic bodies?

Phagocytosed by surrounding cells or macrophages