Autophogy

Question 1

Autophagy

Answer 1

• takes molecules into the cell

- brings into the lysosome to be degraded

Question 2

Macroautophagy

Answer 2

cell engulfs large things outside cell

- autophagosome takes it to the lysosome

Question 3

Microautophagy

Answer 3

Lysosome eats something on its own

Question 4

Chaperone-mediated autophagy

Answer 4

Protein brings molecule to the lysosome

Question 5

Steps of autophagy

Answer 5

• vesicle nucleation of autophagosome
• vesicle elongation of autophagosome
• vesicle fusion of autophagosome
• degradation

Question 6

Where can you inhibit autophagy

Answer 6

Vesicle nucleation
Vesicle elongation
Vesicle fusion

Question 7

When is autophagy induced?

Answer 7

During times of stress

• biggest one is birth (subacute loss of nutrition, e.g. Atg7 knockout mice)
• starvation (e.g. sleeping during night)

Question 8

What are the key roles of autophagy in adults?

Answer 8

• protection against infection and neurodegeneration

- keeps you alive during times of starvation (between meals)

Question 9

What are some functions for (macro)autophagy?

Answer 9

• re-cycle proteins and other macromolecules under conditions of nutrient deprivation
• remove/recycle organelles (mitochondria and peroxisomes)
• allow cell survival under stress conditions)
• regulate antigen presentation to MHC system
• neuro-protection
• remove intracellular pathogens
• remove intracellular pathogens
• aging
• tumor suppression
• tumor promotion
• regulate apoptosis

Question 10

What is an autophagosome?

Answer 10

double membrane vesicle that has already taken up molecules to be degraded that then joins with a lysosome

Question 11

How can autophagy be assessed?

Answer 11

• electromicroscopy
• following autophagosome associated proteins
• western blots
• fluorescent markers (GFP tag)

Question 12

What do ATG genes do?

Answer 12

• regulate autophagy but also other things
• more than 20 gene products required to form autophagosomes
• many of these molecules are potentially druggable

Question 13

Do autophagy regulators do other things independent of autophagy?

Answer 13

yes

Question 14

Are autophagy and apoptosis connected?Provide an example

Answer 14

yes

• caspase cleavage of Beclin amplifies apoptosis
• Beclin-1 functions as part of a protein complex regulated by Bcl-2 and Bcl-xL

Question 15

What does BH3 mimetic ABT 737 do?

Answer 15

• disrupts Beclin-1-Bcl-xl interaction

- affects both pathways - autophagy and apoptosis (trials are starting and don’t understand how affecting both)

Question 16

How does “autophagic” cell death occur?

Answer 16

• associated with formation of autophagic vesicles
• requires autophagic machinery (inhibited by knockdown of Beclin-1/Atg6)
• may be class where autophagy promotes death by making other death mechanisms (apoptosis and necrosis) easier

Question 17

What is the best example of clear autophagy-mediated effect that could be of practical therapeutic relevance?

Answer 17

autophagy as a protection of aggregate prone proteins (e.g. neurodegeneration)

Question 18

How can autophagy protect against neurodegeneration?

Answer 18

• diseases caused by aggregate prone proteins (Alzheimers, Huntington’s)
• increase autophagy - protect in vitro against cell death and in vivo against tissue damage
• can use rapamycin and derivates or other autophagy inducers as chemoprevention/treatment for neurodegenerative diseases

Question 19

What can autophagy protect cells against?

Answer 19

• nutrient deprivation induced stress
• neurodegeneration
• anti-cancer agents