Autophagy

Question 1

What is autophagy?

Answer 1

Autophagy is a process of cell renewal. The cell destroys components of itself (such as proteins, plasma membrane and intracellular organelles) and forms a pool of small molecules (aa, glucose, fatty acids) for energy or reforming cell components

Question 2

In which circumstances does autophagy occur?

Answer 2

When the cell faces starvation, stress, hostile environments or hypoxia. Also occurs to help remove aggregates and misfolded proteins in some degenerative diseases

Question 3

Discuss the genes of autophagy

Answer 3

There are 10-20 genes which control autophagy and are highly conserved across evolution

Question 4

Describe the PROCESS of autophagy

Answer 4

The process is carried out by a prtein complex which can englobe cell particles and form a AUTOPHAGOSOME which then fuses with a lysosome to form a PHAGOLYSOSOME which destroys the cellular components within it and releases small molecules

Question 5

Which signals inhibit autophagy?

Answer 5

Growth signals, RAS pathway, ATP

Question 6

Explain HOW growth signals inhibit autophagy (the mechanism)

Answer 6

They activate mTOR Complex 1 (a kinase) which stays in a complex with ULK1 (which is the ultimate trigger of autophagy). MTORC1 inhibits ULK1 therefore it inhibits autophagy

Question 7

Name signals which would inhibit mTORC1

Answer 7

Starvation
Depletion of proteins
Hypoxia
Stress
Energy depletion

Question 8

Describe the order in which organs undergo autophagy

Answer 8

The first organs to undergo autphagy are the heart and the liver
Next are skeletal muscle and adipose tissue
Some organs never undergo autophagy for energy (such as the neurons in the brain)

Question 9

Describe some other roles autophagy plays

Answer 9

• Essential in embryo development and establishment of the body plan
• Tissue and organ turnover
• Maintainance and disease prevention
• Inhibition of tumour formation

Question 10

What are the roles of ATG5 and ATG6

Answer 10

Autophagy genes essential for embryo development and play a major role in neuronal maintainance

Question 11

Describe evidence of autophagy’s role in inhibiting tumour formation

Answer 11

If autophagy is inactiated in the liver of experimental mice, liver tumours will develope as a result