Autophagy

Question 1

What is autophagy?

Answer 1

Lysosomal clearance of degraded and inappropriate organelles and protein aggregates

Question 2

How does autophagy work? (general outline)

Answer 2

1. Materials to be degraded will be surrounded by a double membrane and form an autophagosome
2. The autophagosome will develop, and fuse with a lysosome to form an autolysosome
3. The materials are degraded in the lysosome

Question 3

What are the 3 types of autophagy?

Answer 3

1. Macroautophagy
2. Microautophagy
3. Chaperone-mediated autophagy

Question 4

What is macroautophagy?

Answer 4

Large-scale degradation of old organelles and materials

Question 5

What is microautophagy?

Answer 5

More specific engulfment and degradation of smaller materials

Question 6

Why is autophagy good and normal?

Answer 6

It maintains homeostasis, and is an adaptation to nutrient stress. It lets cells recycle materials and clear old, damaged organelles that aren’t working properly

Question 7

What 3 things do cells consider to be “dangerous cargo” that needs to be broken down through autophagy?

Answer 7

1. Old, damaged organelles
2. Protein aggregates
3. Intracellular pathogens

Question 8

What are the steps of macroautophagy?

Answer 8

1. The membrane will partially surround the material to be degraded and form a phagophore (initiation and nucleation)
2. The membrane extends through the fusion of tons of small vesicles until it completely surrounds the materials, forming the autophagosome (elongation)
3. The autophagosome then fuses with a lysosome (fusion)
4. The contents are degraded (degradation)

Question 9

What are ATG genes?

Answer 9

Autophagy related genes. The proteins they encode are critical for the formation of the autophagosomes

Question 10

What protein is involved in the initiation step of autophagy? What does it do?

Answer 10

ULK1 complex - a kinase that will phosphorylate targets to signal that autophagy needs to happen

Question 11

What protein is involved in the nucleation step of autophagy? What does it do?

Answer 11

Beclin 1. It is involved in forming the early membrane cup

Question 12

What protein is involved in the elongation step of autophagy? What does it do?

Answer 12

ATG9A. A transmembrane protein that is necessary for a vesicle to fuse with the autophagosome so that it grows around the materials to be degraded

Question 13

What proteins is involved in the fusion step of autophagy? What do they do?

Answer 13

SNAREs, motor proteins, LC3 proteins. These are all needed for the autophagosome to move and to fuse with a target lysosome

Question 14

What two signalling pathways are involved in autophagy?

Answer 14

mTOR and PI3K