Cell death Flashcards
Question 1
What is the final outcome of both the intrinsic and extrinsic apoptotic pathways?
A. Activation of Bcl2 and preservation of the mitochondria
B. Recruitment of p53 and repair of damaged DNA
C. Swelling of the cell and release of its contents
D. Activation of executioner caspases leading to controlled cell death
E. Activation of RIPK1 and MLKL to initiate necrosis
✅ Correct! The answer is D. Activation of executioner caspases leading to controlled cell death
💡 Explanation:
Both the intrinsic (mitochondrial) and extrinsic (death receptor-mediated) apoptotic pathways converge on the activation of executioner caspases (like Caspase-3 and Caspase-7). These enzymes are responsible for cleaving cellular components in an orderly manner, leading to:
DNA fragmentation
Membrane blebbing
Formation of apoptotic bodies
All of which ensure non-inflammatory, controlled cell death — the hallmark of apoptosis.
Question 2
Which of the following accurately describes the role of phosphatidylserine in apoptosis?
A. It forms pores in the mitochondrial membrane
B. It recruits p53 to the nucleus
C. It flips to the outer leaflet of the plasma membrane to signal macrophages
D. It binds to executioner caspases to activate them
E. It is released into the extracellular space to trigger inflammation
C
✅ Correct! The answer is C. It flips to the outer leaflet of the plasma membrane to signal macrophages
💡 Explanation:
In healthy cells, phosphatidylserine (PS) is located on the inner leaflet of the plasma membrane.
During apoptosis, caspases and scramblases cause PS to flip to the outer leaflet. This externalised PS acts as an “eat-me” signal that is recognised by macrophages, prompting them to phagocytose the apoptotic cell — preventing inflammation.
Question 3
Which of the following is a characteristic unique to necrosis and not typically seen in apoptosis?
A. Activation of caspase-3
B. DNA fragmentation at nucleosomes
C. Release of cytochrome c from mitochondria
D. Loss of membrane integrity and inflammatory response
E. Formation of apoptotic bodies
D
✅ Correct again! The answer is D. Loss of membrane integrity and inflammatory response
💡 Explanation:
In necrosis, the cell’s membrane becomes leaky and ruptures, spilling intracellular contents into the surrounding tissue. This causes an inflammatory response.
In contrast, apoptosis maintains membrane integrity and avoids inflammation by packaging the cell into apoptotic bodies that are neatly phagocytosed.
Question 4
Which of the following proteins is responsible for directly fragmenting DNA during apoptosis?
A. Bcl2
B. MLKL
C. iCAD
D. CAD
E. FADD
✅ Correct! The answer is D. CAD
💡 Explanation:
CAD (Caspase-Activated DNase) is the enzyme that directly cleaves DNA between nucleosomes during apoptosis, producing the characteristic DNA ladder pattern.
Normally, CAD is inhibited by iCAD
When executioner caspases are activated, they cleave iCAD, freeing CAD to chop up the DNA
Question 5
Which of the following triggers the intrinsic apoptotic pathway?
A. Binding of Fas ligand to Fas receptor
B. Decreased production of Bcl2 due to absence of survival factors
C. Phosphorylation of MLKL
D. Release of pro-inflammatory cytokines
E. Activation of RIPK3
B. Decreased production of Bcl2 due to absence of survival factors
💡 Explanation:
The intrinsic (mitochondrial) apoptotic pathway is triggered by internal stress, such as:
DNA damage
Lack of growth or survival factors (e.g. nerve growth factor)
This leads to:
↓ Bcl2 (anti-apoptotic protein)
Release of Bax and Bak
Formation of MOMP
Cytochrome c release → Apoptosome → Caspase cascade
🔹 Option C (Phosphorylation of MLKL) refers to necroptosis, not apoptosis.
Question 6
Which protein prevents apoptosis by directly inhibiting Bax and Bak?
A. Caspase-8
B. Apaf-1
C. Bcl2
D. p53
E. FADD
✅ Correct! The answer is C. Bcl2
💡 Explanation:
Bcl2 is an anti-apoptotic protein. It binds to and inhibits Bax and Bak, preventing them from:
Oligomerising on the mitochondrial membrane
Forming MOMP (Mitochondrial Outer Membrane Pores)
Releasing cytochrome c and triggering the intrinsic apoptotic pathway
This makes Bcl2 a key survival factor, and its overexpression is linked to cancer.
Question 7
What is the function of the death-inducing signalling complex (DISC)?
A. Degrades cytochrome c to inhibit apoptosis
B. Activates p53 to induce transcription of Bax
C. Cleaves iCAD to activate CAD
D. Facilitates dimerisation and activation of initiator procaspases
E. Recruits MLKL to form membrane pores
✅ Spot on! The answer is D. Facilitates dimerisation and activation of initiator procaspases
💡 Explanation:
The DISC (Death-Inducing Signalling Complex) is formed in the extrinsic apoptotic pathway after:
Fas ligand binds to the Fas receptor
FADD is recruited
Procaspase-8 molecules are brought close together
They dimerise and self-cleave → active initiator caspases
These then go on to activate executioner caspases, triggering apoptosis.
Question 8
Which of the following correctly describes a function of p53 in apoptosis?
A. Phagocytoses apoptotic bodies
B. Inhibits cytochrome c release
C. Stimulates production of anti-apoptotic proteins
D. Activates transcription of pro-apoptotic BH3-only proteins
E. Forms the apoptosome
✅ Correct! The answer is D. Activates transcription of pro-apoptotic BH3-only proteins
💡 Explanation:
In response to DNA damage, the tumour suppressor p53 is activated and:
Promotes transcription of BH3-only proteins (a subclass of pro-apoptotic proteins)
These BH3-only proteins inhibit Bcl2, freeing Bax and Bak
This leads to MOMP, cytochrome c release, and activation of the intrinsic apoptotic pathway
So, p53 acts as a key pro-apoptotic regulator when a cell is too damaged to be repaired.
Question 9
Which of the following is not a feature of apoptosis?
A. Cell shrinkage
B. Activation of caspases
C. Inflammatory response
D. Chromatin condensation
E. DNA cleavage at nucleosomes
✅ Absolutely right! The answer is C. Inflammatory response
💡 Explanation:
Apoptosis is a clean and controlled process:
The cell shrinks, not swells
Caspases are activated
Chromatin condenses, DNA is cut between nucleosomes
Apoptotic bodies form and are phagocytosed
Crucially: no contents are released → no inflammation
In contrast, necrosis causes cell lysis and triggers inflammation.
Question 10
Which protein is directly responsible for forming pores in the mitochondrial outer membrane during intrinsic apoptosis?
A. Apaf-1
B. Bak
C. Bcl2
D. Caspase-3
E. MLKL
B The correct answer is B. Bak
💡 Explanation:
During intrinsic apoptosis, the pro-apoptotic proteins Bak and Bax:
Oligomerise in the mitochondrial outer membrane
Form the MOMP (Mitochondrial Outer Membrane Pore)
This allows cytochrome c to escape into the cytosol → apoptosome formation
🔹 Option E (MLKL) is involved in necroptosis, not apoptosis — it forms plasma membrane pores, not mitochondrial ones.
Question 11
Which caspase is classified as an initiator caspase in the intrinsic apoptotic pathway?
A. Caspase-3
B. Caspase-7
C. Caspase-8
D. Caspase-9
E. Caspase-1
D
D. Caspase-9
💡 Explanation:
In the intrinsic (mitochondrial) pathway:
DNA damage → cytochrome c release
Cytochrome c + Apaf-1 → Apoptosome
Apoptosome activates Caspase-9 → the initiator caspase
Caspase-9 then activates executioner caspases like Caspase-3 and Caspase-7
🔹 Caspase-8 (your choice) is the initiator caspase for the extrinsic pathway — you’re very close!
Question 12
Which of the following is true about necroptosis, but not apoptosis?
A. Requires active caspases
B. Involves the apoptosome
C. Depends on cytochrome c release
D. Leads to inflammatory response
E. Is triggered by DNA damage
✅ Correct! The answer is D. Leads to inflammatory response
💡 Explanation:
Necroptosis is a form of regulated necrosis that:
Results in membrane rupture
Releases intracellular contents
Triggers an inflammatory response, just like necrosis
In contrast, apoptosis is non-inflammatory because:
The membrane stays intact
The cell is packaged into apoptotic bodies
These are cleared by macrophages with no spill-over
Question 13
Which enzyme cleaves iCAD, thereby enabling DNA fragmentation in apoptosis?
A. Caspase-9
B. Caspase-3
C. CAD
D. FADD
E. Bax
B. Caspase-3
💡 Explanation:
Caspase-3 is a key executioner caspase in apoptosis. It:
Cleaves iCAD (the inhibitor of CAD)
This releases CAD, a DNase that cuts DNA between nucleosomes
Result: classic DNA fragmentation or “laddering” pattern seen in apoptotic cells
🔹 Bax is a pro-apoptotic protein, but it acts earlier — by helping form the MOMP, not by cleaving iCAD.
Question 14
Which of the following correctly describes the role of Apaf-1?
A. Cleaves executioner caspases
B. Inhibits Bax/Bak oligomerisation
C. Forms the DISC complex
D. Recruits procaspase-9 into the apoptosome
E. Prevents formation of apoptotic bodies
D. Recruits procaspase-9 into the apoptosome
💡 Explanation:
Apaf-1 (Apoptotic Protease Activating Factor 1) plays a central role in the intrinsic pathway:
Binds to cytochrome c in the cytosol
Oligomerises to form the apoptosome
The apoptosome then recruits and activates procaspase-9 → initiates the caspase cascade
🔹 Option C refers to the DISC, which is involved in the extrinsic pathway, and is formed by Fas receptor + FADD + procaspase-8
Question 15
Which of the following best explains why necrosis is often observed in the centre of solid tumours?
A. Excess Bcl2 expression in central tumour cells
B. Activation of caspase-8 by cytotoxic T-cells
C. Accumulation of macrophages in the tumour periphery
D. Lack of blood supply leads to hypoxia and ATP depletion
E. Presence of high concentrations of survival factors
✅ Correct! The answer is D. Lack of blood supply leads to hypoxia and ATP depletion
💡 Explanation:
In solid tumours, the centre often becomes:
Ischaemic (poor blood supply)
Hypoxic (low oxygen)
Nutrient-deprived
This results in ATP depletion, which means:
The cell cannot perform apoptosis (which is ATP-dependent)
Instead, it undergoes necrosis, leading to inflammation and tissue damage
This necrotic core is a hallmark of rapidly growing, poorly vascularised tumours.
Question 16
Which of the following proteins is phosphorylated and oligomerises to form pores in the plasma membrane during necroptosis?
A. FADD
B. RIPK1
C. RIPK3
D. MLKL
E. Apaf-1
D. MLKL
💡 Explanation:
In necroptosis:
Death receptor is activated
RIPK1 and RIPK3 interact and activate each other
RIPK3 phosphorylates MLKL
Phosphorylated MLKL oligomerises and forms pores in the plasma membrane
This causes cell swelling, rupture, and inflammation
🔹 RIPK3 is upstream in the pathway — it doesn’t form the pore itself.
Question 17
Which of the following best explains why apoptosis is non-inflammatory?
A. It activates immune suppressor cells
B. It suppresses mitochondrial membrane rupture
C. It keeps phosphatidylserine on the inner leaflet
D. It involves rapid phagocytosis of apoptotic bodies
E. It inhibits cytokine release by T-cells
D. It involves rapid phagocytosis of apoptotic bodies
💡 Explanation:
Apoptosis avoids inflammation by:
Maintaining membrane integrity
Fragmenting the cell into apoptotic bodies
These are rapidly recognised and engulfed by nearby macrophages
No intracellular contents are spilled → no inflammatory response
🔹 Option B (mitochondrial membrane rupture) does occur during intrinsic apoptosis to release cytochrome c, but this is a controlled process and doesn’t lead to inflammation.
Question 18
What is the main role of survival factors in regulating apoptosis?
A. They stimulate formation of apoptotic bodies
B. They suppress p53 transcription
C. They promote the synthesis of Bcl2
D. They activate executioner caspases
E. They phosphorylate MLKL to block necroptosis
c
✅ Correct! The answer is C. They promote the synthesis of Bcl2
💡 Explanation:
Survival factors (e.g., nerve growth factor) are secreted by neighbouring cells and:
Bind to receptors on the target cell
Trigger intracellular signalling pathways
This upregulates Bcl2, an anti-apoptotic protein
Bcl2 inhibits Bax/Bak, preventing MOMP and apoptosis
This mechanism ensures that only cells receiving enough support survive — particularly important during development.
Question 19
Which of the following is responsible for activating initiator caspase-9 in the intrinsic pathway?
A. DISC
B. Apoptosome
C. FADD
D. MLKL
E. iCAD
B. Apoptosome
💡 Explanation:
In the intrinsic pathway:
Cytochrome c is released from mitochondria
It binds with Apaf-1 to form the apoptosome
The apoptosome then recruits and activates procaspase-9
Caspase-9 then activates executioner caspases → apoptosis
🔹 DISC (your answer) is formed in the extrinsic pathway, not intrinsic. It activates caspase-8, not caspase-9.
Question 20
Which of the following best describes the consequence of excessive Bcl2 expression in a cell?
A. Increased phagocytosis of apoptotic cells
B. Enhanced formation of apoptosomes
C. Prevention of MOMP and inhibition of apoptosis
D. Activation of CAD and DNA fragmentation
E. Stimulation of MLKL and plasma membrane pore formation
The answer is C. Prevention of MOMP and inhibition of apoptosis
💡 Explanation:
Bcl2 is an anti-apoptotic protein. When overexpressed, it:
Binds to Bax and Bak, keeping them inactive
Prevents formation of MOMP (mitochondrial outer membrane pores)
Blocks cytochrome c release
Therefore, intrinsic apoptosis is halted
This is commonly seen in cancer cells, which evade death by overproducing Bcl2 — and can be targeted by drugs like Venetoclax.
