Autophagy

Question 1

The maintenance of proteins in their proper amounts, locations, associations and folded states

Answer 1

Proteostasis

Question 2

List the steps of autophagy.

Answer 2

Initiation by phagophore / isolation membrane (double) enriched in PI3P
Vesicle elongation
Maturation into autophagosome
Docking and fusion of lysosome to create autolysosome
Vesicle breakdown and degradation

Question 3

What are the three forms of autophagy that regulate turnover of cellular material?

Answer 3

1. ) Macroautophagy (standard)
2. ) Chaperone-mediated autophagy (tagged proteins require chaperone to dock and fuse to lysosome)
3. ) Microautophagy (invagination of lysosomal membrane)

Question 4

Define autophagy y

Answer 4

the catabolic sequestration and degradation of a wide array of cellular and foreign material

Question 5

Double-membrane bound organelles that fuse with lysosomes

Answer 5

Autophagosome

Question 6

How does regulated machinery govern autophagosome maturation?

Answer 6

Small ubiquitin-like molecules are attached to autophagosome during elongation to allow maturation.

Question 7

What role to autophagy receptors play?

Answer 7

Allow selective recruitment of specific and diverse cargo into autophagosomes

Question 8

How does autophagy relate between yeast and humans?

Answer 8

Very high conserved

Ancient mechanism for sequestering and degrading material

Question 9

What upstream signals regulate autophagy induction?

Answer 9

Autophagy-promoting: 
Energy depletion
Starvation 
Rapamycin 
Beclin 1

Autophagy-inhibiting: 
Nutrient signals
Insulin 
Growth factor signaling 
BCL2

Question 10

How is autophagy required for normal mammalian development?

Answer 10

Necessary for embryogenesis

autophagy induced after fertilization

Question 11

How can autophagy inhibit tumorigenesis?

Answer 11

Autophagy suppresses tumorigenesis after stress (such as oxidative stress that might lead to mutations)
Damaged proteins and organelles are eliminated

Question 12

How can autophagy confer stress resistance on established tumors?

Answer 12

Autophagy allows for cell survival and tumor growth in hypoxic tumor regions

Question 13

How is autophagy involved in bacterial infection?

Answer 13

Autophagy protects the host (targets bacteria and viruses for destruction)
Can also be subverted by pathogens (various toxins interfere with steps of autophagy)

Question 14

How does autophagy normally protect against neurodegeneration?

Answer 14

Autophagy clears protein aggregates
Aggregation and loss of proteostasis common theme in these diseases
Autophagy is impaired in several of these diseases
Alzheimer’s
Parkinson’s