Cell Death

Question 1

What is one of the main triggers for cell death?

Answer 1

DNA damage specifically DNA double stranded breaks

Question 2

What makes cancer cells difficult to kill?

Answer 2

Lack of cell cycle control

Question 3

Describe the morphological characteristics of necrosis

Answer 3

Cell membrane swelling and rupture
Cytoplasm: increased vacuolation, organelle degeneration and mito swelling
Nucleus: clumping and degradation of chromatin/DNA

Question 4

Which cells are involved in necrosis and is inflammation present?

Answer 4

All cell types involved

Inflammation present

Question 5

What are the biochemical features that lead to necrosis?

Answer 5

Extensive failure of normal physiological pathways that are essential for maintaining cellular homeostasis such as regulation of ion transport, energy production and pH balance

Question 6

Describe some necrosis mechanisms

Answer 6

Two key players: RIP1 and PARP1
Ca2+ overload, mito uncoupling, increased O2 consumption, excessive ROS production, ATP depletion
NO caspases involved

Question 7

Describe the morphological characteristics of apoptosis

Answer 7

Cell membrane: blebbing and fragmentation into apoptotic bodies
Cytoplasm: fragmentation and shrinkage
Nucleus: chromatin condensation and degradation -> nuclear fragmentation

Question 8

Which cells are involved in apoptosis and is inflammation present?

Answer 8

Hematopoietic cells and their malignant counterparts (liquid tumors)
NO inflammation

Question 9

Describe the biochemical features that may result in apoptosis

Answer 9

Cell membrane loses its asymmetry and phosphatidylserine becomes exposed on the cell surface
Caspases and mitochondria dependent

Question 10

What are some apoptosis mechanisms?

Answer 10

DNA damage (ATM and p53)
Death receptor signaling (TNF and Fas) 
Activation of sphingomyelinase 
Mito damage mediated by ceramide 
Bax and Bak

Question 11

Describe the role Bax and Bak play in apoptosis

Answer 11

Though to induce permeabilization by forming pores upon oligomerization
Pro-apoptotic BH3 only family membranes can activate Bax/Bak by either binding to anti-apoptotic Bcl2 or the BH3 proteins can directly bind and activate Bax/Bak

Question 12

What are the sensors and mediators of apoptosis?

Answer 12

Sensors: ATM, receptor, mitochondria
Mediators: p53, Bcl2, pro-apoptotic BH3 and Bax fam, cyt c, apoptotic protease activating factor 1 (APAF1)

Question 13

What are the effectors of apoptosis?

Answer 13

Initiators: caspase 8, 9 and 10
Executioners: caspase 3, 6 and 7

Question 14

Which members of the BH3 only family can activate Bax/Bak?

Answer 14

Bad, Bid, Bim, Puma and Noxa

Question 15

What is autophagy?

Answer 15

A process responsible for degrading long lived proteins and cytoplasm organelles to maintain cellular homeostasis
Most a survival mechanism in response to several stresses (like DNA damage, protein aggregation, pathogens and nutrient starvation)

Question 16

Describe the morphological characteristics of autophagy

Answer 16

Cell membrane: blebbing
Cytoplasm: accumulation of 2 autophagic vacuoles
Nucleus: partial chromatin condensation, no fragmentation

Question 17

Which cell types are involved in autophagy and is inflammation present?

Answer 17

All cell types involved

No inflammation

Question 18

Biochemical features of autophagy?

Answer 18

Caspase independent and increased lysosomal activity

Question 19

What are the major players in autophagy?

Answer 19

Autophagy related genes (Atg)
Coiled-coil myosin like Bcl2 interacting protein (Beclin-1)(Atg-6) - initiation of the formation of the autophagosome (nucleation)
Microtubule associated protein 1A/B light chain 3 (LC3) - conjugation and elongation

Question 20

What is mitotic catastrophe?

Answer 20

A type of cell death caused by aberrant mitosis and is associated with deficiencies in cell cycle checkpoints in mammals

Question 21

Describe the morphological characteristics in mitotic catastrophe

Answer 21

No change in cell membrane 
Large cytoplasm (giant cell) 
Nucleus: micro and multinucleation, nuclear fragmentation

Question 22

Which cells are involved in mitotic catastrophe and is inflammation present?

Answer 22

Most dividing cells involved

No inflammation

Question 23

What are the biochemical features of mitotic activation?

Answer 23

Caspase independent (at early stage) and abnormal Cdk1/cyclin B activation

Question 24

What are the mechanisms of mitotic catastrophe?

Answer 24

Defects in cell cycle checkpoints
Hyperamplification of centrosomes
Caspase 2 activation during metaphase

Question 25

What is the fate of cells with aberrant mitosis?

Answer 25

Mitotic death (die without mitosis)
Delayed cell death
Senescence (exit mitosis and undergo permanent G1 arrest)

Question 26

What is senescence?

Answer 26

Permanent cell cycle arrest and reproductive death

Can be replicative related to telomere shortening

Question 27

Describe the morphological characteristics of senescence

Answer 27

No change in cell membrane
Cytoplasm: flat and granular
Nucleus: distinct heterochromatic structure

Question 28

What cell types are involved in senescence and is inflammation present?

Answer 28

All cell types involved

Inflammation present but induced secretory factors from the senescent cell itself

Question 29

What mechanism is used in senescence?

Answer 29

Same as DNA damage responses that activate cell cycle checkpoints (ex. ATM pathway)
Two pathways that lead to the same fate (growth arrest): p53-p21 and p16-Rb