Autophagy

Question 1

macroautophagy

Answer 1

Formation of a double-membraned vesicle (autophagosome) containing organelles etc.
Will fuse with lysosome and will be degraded

Question 2

chaperone-mediated autophagy

Answer 2

Recognition of specific proteins that contain a specific recognition sequence (based on KFERQ) and direct binding and delivery to lysosomes

Question 3

describe process of macroautophagy

Answer 3

1. Induction: nutrient starvation, growth factor mediated starvation, exposure to drugs, rapamycin
2. Vesicle nucleation (phagophore) via PI3K activation
3. Vesicle expansion (omegasome)
4. Cargo targeting
5. Vesicle closure (autophagosome)
6. Vesicle fusion with endosome (amphisome)
7. Vesicle fusion with lysosomes ( autolysosome)

Question 4

rationale behind autophagy’s protective action against neurodegeneration.

Answer 4

Neurodegeneration caused by protein aggregation–> cell death/tissue damage

Autophagy clears proteins that can aggregate
–> provides protection again neuro degeneration

Question 5

mechanisms by which apoptosis induction and autophagy are connected.

Answer 5

Same proteins can regulate the two processes (among other things)
-ie Bcl-2
It is difficult to tell which process is affecting which

Ie.

1. Apoptosis can regulate autophagy
   - caspase (apoptotic protease) can cleave essential autophagy regulators, inactivating them, and blocking autophagy

Question 6

How do we detect autophagy in the lab?

Answer 6

Via electron microscopy

Or GFP tagging

Question 7

What are two results of macroautophagy?

Answer 7

Recycling cytoplasmic components

Boost energy generation during nutrient deprivation

Question 8

Beclin 1

Answer 8

Autophagy gene - haplo insufficient tumor suppressor in mice

Question 9

Does autophagy support tumor growth or suppression?

Answer 9

Both yo. ( he spent 5 min on this during lecture)

Question 10

When is autophagy activated?

Answer 10

During times of stress (ie. Nutrient deprivation ect.)

Occurring all the time

Question 11

Atg genes

Answer 11

Many different types

Regulates autophagy

Question 12

Motif for CMA? What protein delivers proteins into the lysosome?

Answer 12

KFERQ motif

LAMP-2A

Question 13

Shorter lived proteins degraded by? Longer lived proteins?

Answer 13

Short-lived: proteasome
Long-lived and organelles: autophagy
Lysosomes and peroxisomes: mitophagy

Question 14

P62 and NBR1 and NDP52

Answer 14

Cargo recognition proteins

Question 15

Does autophagy stimulate cell death?

Answer 15

Unclear evidence, cells prefer to die by apoptosis if possible.

Autophagy may promote death by making other death mechanisms easier ( apoptosis or necrosis)