Cell Death

Question 1

What are the three cell fates in the cycle?

Answer 1

• Normal function without dividing (G0/G1)
• Somatic cell division
• Cell death (apoptosis)

Question 2

When does cell death occur?

Answer 2

At the end of a cell’s natural lifespan via activation of a built-in “suicide” programme (apoptosis)

Question 3

What happens in G1 phase?

Answer 3

Cellular contents (excluding chromosomes) are duplicated

Question 4

What happens in S phase?

Answer 4

Each of the 46 chromosomes is duplicated

Question 5

What happens in G2 phase?

Answer 5

Cell double-checks duplicated chromosomes for errors and repairs them

Question 6

What happens in M phase?

Answer 6

Mitosis and cytokinesis occur

Question 7

What is cell cycle arrest?

Answer 7

A pause in the cycle due to damage or lack of division signals

Question 8

Why does cell death occur naturally?

Answer 8

• To regulate cell populations
• To remove damaged or dangerous cells

Question 9

What are examples of regulated cell death?

Answer 9

• Replicating tissues (homeostasis)
• Embryonic development (excess cells)
• Immune system (obsolete cells)
• Post-natal changes (e.g. post-pregnancy)

Question 10

What are examples of damage-triggered cell death?

Answer 10

• Virus-infected cells
• Potential cancer cells

Question 11

What is apoptosis?

Answer 11

A tightly controlled form of programmed cell death that eliminates unneeded or unwanted cells

Question 12

Why is apoptosis important?

Answer 12

• Maintains cell and tissue turnover
• Shapes development (e.g. fingers)
• Removes damaged cells (e.g. sunburn)

Question 13

What are the two types of apoptosis control signals?

Answer 13

• Blocking signals — promote survival
• Promoting signals — promote death

Question 14

What are examples of apoptosis blocking signals?

Answer 14

• Growth hormones
• Growth factors
• Contact with other cells

Question 15

What do blocking signals do?

Answer 15

Prevent cell destruction by maintaining survival signals

Question 16

What are examples of apoptosis promoting signals?

Answer 16

• Loss of survival signals
• DNA damage
• Errors in cell division
• Activation of death receptors

Question 17

How do promoting signals work?

Answer 17

Override survival signals and activate suicide genes (e.g. Bax

Question 18

What are the four phases of optic nerve development?

Answer 18

• Optic stalk extension
• Choroidal fissure closure (coloboma)
• Migration of retinal ganglion cell axons to LGN
• Reduction of axons by apoptosis (megalopapilla)

Question 19

When does myelination of optic nerve axons occur?

Answer 19

Later in gestation (~32 weeks in humans)

Question 20

What are the steps of apoptosis?

Answer 20

• Mitochondria leak cytochrome C
• Cytochrome C activates caspase enzymes
• Caspases dismantle cell contents
• Cell shrinks and detaches
• Macrophages engulf and recycle the cell

Question 21

What are visible changes during apoptosis?

Answer 21

• Membrane blebbing
• Organelle disintegration
• Chromatin condensation
• Formation of apoptotic bodies
• No inflammation

Question 22

What are the two main pathways of apoptosis?

Answer 22

• Extrinsic pathway — external death receptors
• Intrinsic pathway — internal damage (e.g. DNA)

Question 23

What is the common final route of apoptosis?

Answer 23

Activation of caspase 3 and caspase 7

Question 24

What triggers the extrinsic pathway?

Answer 24

• Death receptors (e.g. TRAILR

Question 25

What proteins are involved in the extrinsic pathway?

Answer 25

* FADD * Pro-caspase-8 and -10 * Caspase-3 and -7 * Granzyme B * Adapter proteins

Question 26

What triggers the intrinsic pathway?

Answer 26

* DNA damage * ER stress * Hypoxia * Metabolic stress * Radiation * Toxins * Free radicals

Question 27

What proteins are involved in the intrinsic pathway?

Answer 27

• BCL-2 family (BCL-X

Question 28

How is apoptosis studied?

Answer 28

• Microscopy — cell blebbing

Question 29

What is necrosis?

Answer 29

Uncontrolled cell death due to injury or disease (e.g. gangrene)

Question 30

What happens during necrosis?

Answer 30

* Cell swells and ruptures * Membrane breakdown releases lysosomal enzymes * Enzymes damage surrounding cells * Debris accumulates → pus * Inflammatory response triggered

Question 31

What are the stages of necrosis?

Answer 31

* Reversible injury → swelling of ER and mitochondria * Progressive injury → membrane breakdown

Question 32

How do apoptosis and necrosis differ?

Answer 32

• Apoptosis: normal

Question 33

What do apoptosis and necrosis have in common?

Answer 33

• Stimulated by cytokines

Question 34

What happens when apoptosis control is faulty?

Answer 34

Imbalance between cell proliferation and death

Question 35

What are effects of excessive apoptosis?

Answer 35

* Loss of tissue mass * Alzheimer’s Disease * Parkinson’s Disease * AIDS * Macular degeneration

Question 36

What are effects of underactive apoptosis?

Answer 36

* Increase in tissue mass * Cancer (e.g. retinoblastoma) * Developmental failure

Question 37

How do cancer cells evade apoptosis?

Answer 37

* Accumulate genetic changes for survival * Amplify anti-apoptotic machinery * Suppress pro-apoptotic programs

Question 38

What is the role of Rb protein in cell cycle regulation?

Answer 38

* Non-phosphorylated Rb binds E2F → blocks transcription * Phosphorylation of Rb releases E2F → enters nucleus * E2F activates transcription of cell cycle proteins

Question 39

What happens when Rb gene is mutated?

Answer 39

Leads to uncontrolled cell cycle progression and retinal cancer

Question 40

What are the review questions?

Answer 40

* How does cell death by apoptosis protect other cells? * How does necrosis damage tissues? * How do cancer cells evade apoptosis?