Cell Death

Question 1

What is the process called when cells die at the same rate as they are produced?

Answer 1

Cell turnover

Question 2

What is apoptosis?

Answer 2

A molecularly distinct form of cell suicide occurring only in animal cells

Question 3

How does apoptosis differ from necrosis?

Answer 3

Apoptosis is a controlled process, while necrosis is often uncontrolled and leads to inflammation

Question 4

What are the characteristic morphological changes of a cell undergoing apoptosis?

Answer 4

• Cell shrinkage
• Cytoskeleton collapse
• Nuclear envelope disassembly
• Chromatin condensation and fragmentation

Question 5

What are apoptotic bodies?

Answer 5

Membrane-enclosed fragments formed from a large apoptotic cell

Question 6

Which type of cells typically engulf apoptotic cells?

Answer 6

Macrophages

Question 7

What is the role of apoptosis in the vertebrate adaptive immune system?

Answer 7

Eliminates developing T and B lymphocytes that are nonfunctional or potentially dangerous

Question 8

What initiates the apoptotic program in mammals?

Answer 8

Initiator caspases, mainly caspase-8 and caspase-9

Question 9

What is the function of executioner caspases?

Answer 9

Orchestrate the apoptosis program by cleaving specific target proteins

Question 10

What are the two main activation pathways for initiator caspases?

Answer 10

• Extrinsic pathway
• Intrinsic pathway

Question 11

What is the significance of phosphatidylserine exposure on the surface of apoptotic cells?

Answer 11

It serves as an ‘eat me’ signal for phagocytic cells

Question 12

What regulates the balance of cell death and cell division in adult tissues?

Answer 12

Tight regulation of both cell death rate and cell birthrate

Question 13

What is the role of caspase-1?

Answer 13

Stimulates inflammatory responses by cleaving precursors of pro-inflammatory cytokines

Question 14

What is the result of cleaving nuclear lamins during apoptosis?

Answer 14

Irreversible breakdown of the nuclear lamina

Question 15

What change occurs to the actin cytoskeleton during apoptosis?

Answer 15

Actin polymerization in the cell cortex leading to surface blebbing

Question 16

What are executioner caspases?

Answer 16

Executioner caspases are activated by cleavage, have short prodomains, and cleave various cell target proteins to induce apoptosis.

Question 17

How are executioner caspases activated?

Answer 17

They are activated by cleavage at a site in each protease domain, usually by an initiator caspase.

Question 18

What role does caspase-3 play in apoptosis?

Answer 18

Caspase-3 activates DNase by cleaving its inhibitor, iCAD, leading to DNA fragmentation.

Question 19

What is the function of caspase-activated DNase (CAD)?

Answer 19

CAD cuts chromosomal DNA between nucleosomes during apoptosis.

Question 20

What triggers the extrinsic pathway of apoptosis?

Answer 20

Extracellular signal proteins binding to cell-surface death receptors trigger the extrinsic pathway.

Question 21

What are death receptors?

Answer 21

Transmembrane proteins with a ligand-binding domain, a transmembrane domain, and an intracellular death domain.

Question 22

Name a well-known example of a death receptor.

Answer 22

Fas death receptor.

Question 23

What is the role of Fas ligand in apoptosis?

Answer 23

Fas ligand binds to Fas receptors, clustering them and activating apoptosis.

Question 24

What is the function of FADD in the extrinsic pathway?

Answer 24

FADD binds to exposed death domains on Fas receptors and recruits initiator caspase-8.

Question 25

What is the function of FLIP in the extrinsic pathway?

Answer 25

FLIP inhibits caspase-8 activation, preventing apoptosis.

Question 26

What is the intrinsic pathway of apoptosis also known as?

Answer 26

The mitochondrial pathway.

Question 27

What key protein is released from mitochondria during the intrinsic pathway?

Answer 27

Cytochrome c.

Question 28

What does cytochrome c bind to in the cytosol?

Answer 28

Apaf1 (apoptotic protease activating factor 1).

Question 29

What structure is formed when cytochrome c binds to Apaf1?

Answer 29

An apoptosome.

Question 30

What is the role of caspase-9 in the intrinsic pathway?

Answer 30

Caspase-9 is activated within the apoptosome and cleaves executioner caspases.

Question 31

What family of proteins regulates the intrinsic pathway?

Answer 31

Bcl2 family of proteins.

Question 32

What is the primary function of Bcl2 proteins?

Answer 32

They control the permeabilization of the outer mitochondrial membrane.

Question 33

What is a monomer?

Answer 33

A single molecule that can join together with others to form a polymer.

Question 34

What is the function of caspase-9?

Answer 34

It is an initiator caspase involved in the activation of executioner caspases.

Question 35

What is a dimer?

Answer 35

A molecule composed of two identical or similar subunits.

Question 36

What is mitochondrial outer membrane permeabilization (MOMP)?

Answer 36

A process that allows proteins from the intermembrane space to enter the cytosol.

Question 37

Name the three structural and functional classes of mammalian Bcl2 family proteins.

Answer 37

* Anti-apoptotic Bcl2 family proteins * Pro-apoptotic Bcl2 family effectors * BH3-only proteins

Question 38

What role do anti-apoptotic Bcl2 family proteins play?

Answer 38

They inhibit apoptosis by preventing mitochondrial outer membrane permeabilization.

Question 39

What do pro-apoptotic Bcl2 family effectors do?

Answer 39

They induce MOMP by creating openings in the outer mitochondrial membrane.

Question 40

What is the role of BH3-only proteins?

Answer 40

They promote apoptosis by regulating the activities of other Bcl2 family proteins.

Question 41

How do BH3-only proteins trigger apoptosis?

Answer 41

They can inhibit anti-apoptotic proteins or activate Bak and Bax.

Question 42

What happens when cytochrome c is released into the cytosol?

Answer 42

It stimulates the assembly of apoptosomes.

Question 43

What is the function of XIAP?

Answer 43

It inhibits caspase-9, caspase-3, and caspase-7 in the cytosol.

Question 44

What is the role of extracellular survival factors?

Answer 44

They inhibit apoptosis and promote cell survival.

Question 45

What triggers the activation of BH3-only proteins like Puma and Noxa?

Answer 45

Accumulation of the tumor suppressor protein p53 in response to DNA damage.

Question 46

What is the function of the BH3 domain?

Answer 46

It mediates the direct interactions between pro-apoptotic and anti-apoptotic Bcl2 family members.

Question 47

What mechanism do IAP proteins use to inhibit apoptosis?

Answer 47

They bind to and inhibit caspases, preventing their activation.

Question 48

What is the significance of the balance between anti-apoptotic and pro-apoptotic proteins?

Answer 48

It determines whether a cell undergoes apoptosis or survives.

Question 49

What do most animal cells require to avoid undergoing apoptosis?

Answer 49

Signals from other cells ## Footnote This is usually mediated by the intrinsic pathway.

Question 50

How do nerve cells compete for survival during development?

Answer 50

They compete for limited amounts of survival factors secreted by target cells ## Footnote This ensures that only the necessary number of neurons survive.

Question 51

What is the role of survival factors in preventing apoptosis?

Answer 51

They bind to cell-surface receptors and activate intracellular signaling pathways that suppress the apoptotic program.

Question 52

Name a type of protein that survival factors stimulate to prevent apoptosis.

Answer 52

Anti-apoptotic Bcl2 family proteins ## Footnote Examples include Bcl2 and BclxL.

Question 53

What is the process by which apoptotic cells are removed from the body?

Answer 53

Phagocytosis by neighboring cells ## Footnote Typically, this process is performed by macrophages.

Question 54

What is the most important 'eat me' signal displayed by apoptotic cells?

Answer 54

Phosphatidylserine (PS)

Question 55

How is phosphatidylserine (PS) normally kept within healthy cells?

Answer 55

By a specific phospholipid flippase that uses ATP hydrolysis.

Question 56

What happens to the flippase during apoptosis?

Answer 56

It is cleaved and inactivated by executioner caspases.

Question 57

What can excessive apoptosis lead to?

Answer 57

Pathological tissue loss ## Footnote Examples include heart attacks and strokes.

Question 58

What is a consequence of insufficient apoptosis in humans?

Answer 58

Abnormal accumulation of lymphocytes, leading to autoimmune disorders.

Question 59

Name a gene that, when mutated, contributes to decreased apoptosis in cancer.

Answer 59

p53

Question 60

What is the primary function of apoptotic caspases?

Answer 60

To cleave specific intracellular proteins to kill the cell quickly and neatly.

Question 61

What happens to the cell during apoptosis?

Answer 61

The cell shrinks, the nucleus condenses and fragments, and is engulfed by phagocytic cells.

Question 62

Fill in the blank: Apoptosis is mediated by _______ enzymes called caspases.

Answer 62

Proteolytic

Question 63

What is apoptosis?

Answer 63

A programmed cell death process mediated by caspases.

Question 64

What are caspases?

Answer 64

Proteolytic enzymes that mediate apoptosis by cleaving specific intracellular proteins.

Question 65

How are apoptotic caspases present in cells?

Answer 65

As inactive precursors in almost all nucleated animal cells.

Question 66

What activates initiator caspases?

Answer 66

Apoptotic stimuli activate adaptor proteins that bring inactive initiator caspase monomers into proximity.

Question 67

What is the role of activated initiator caspase dimers?

Answer 67

They cleave themselves and activate downstream executioner caspase dimers.

Question 68

What do executioner caspases do?

Answer 68

They cleave hundreds of target proteins in the cell.

Question 69

What is the caspase cascade?

Answer 69

An amplifying, irreversible process responsible for all events of apoptosis.

Question 70

What are the two distinct pathways to activate initiator caspases?

Answer 70

Extrinsic pathway and intrinsic pathway.

Question 71

What activates the extrinsic pathway?

Answer 71

Extracellular ligands binding to cell-surface death receptors.

Question 72

What activates the intrinsic pathway?

Answer 72

Developmental signals or stress signals from within the cell.

Question 73

What is the role of the DISC in apoptosis?

Answer 73

It's an activation complex formed by the recruitment of caspase-8 via adaptor proteins in the extrinsic pathway.

Question 74

What happens during mitochondrial outer membrane permeabilization (MOMP)?

Answer 74

Soluble proteins are released from the mitochondrial intermembrane space into the cytosol.

Question 75

What does cytochrome c do in the intrinsic pathway?

Answer 75

It activates the adaptor protein Apaf1, which recruits caspase-9 monomers to form the apoptosome.

Question 76

What is the apoptosome?

Answer 76

A large activation complex formed in the intrinsic pathway that involves caspase-9.

Question 77

What is the function of Bcl2 family proteins in apoptosis?

Answer 77

They tightly control MOMP to regulate the intrinsic pathway of apoptosis.