Autophagy

Question 1

What are the types of autophagy?

Answer 1

macrophagy, chaperone-mediated autophagy (2 most important)

and microautophagy

Question 2

Name at least 5 functions of (macro)autophagy

Answer 2

• Recycle proteins and other macro molecules
• remove organelles
• Allow cell survival under stress conditions
• Present antigens to MHC (Major histone compatibility complex)
• Neuro-protection
• Remove intracellular pathogens
• Age increased autophagy can extend life
• Tumor supression
• Tumor promotion (req for progression and metastasis
• inhibit apoptosis- but kill cells

Question 3

What are the steps of the autophagic process?

Answer 3

1. Induction (nutrient starvation, GF mediated starvation, exposure to chemo, rapamycin, etc)
2. Vesicle nucleation (phagospore)
3. Vesicle expansion (omegasome)
4. Cargo targeting (by LC3II and p62)
5. Vesicle closure (autophagosome)
6. Fusion with endosome (amphisome
7. Vesicle fusion with lysosome (autolysosome)

Question 4

Describe macrophagy

Answer 4

double membrane vesicle captures cytosolic components/ organelles
- fuse with lysosome where hydrolases degrade contents of autophagosome

• Activation of P13K complex that allows nucleation of membrane eventually forming autophagosome
• regulation of protein conjugation events to extend membrane
• randomly capture or specifically deliver cago to extending autophagosome- > join membranes to close vesicle
• fuse with lysosome
• recycle aa and other macromolecular precurssors

Question 5

Describe chaperone mediated autophagy

Answer 5

recognition of protein containing KFERQ aa motif

- direct binding and delivery to lysosome

Question 6

Describe the rationale behind autophagy’s protective action against neurodegeneration

Answer 6

Aggregate prion proteins (expanded stretches of glutamine residues in diseases like huntington’s) will cause neuronal cell death

• Autophagy degrades aggregate prone proteins (maybe after beginning to form small aggregates
• no toxic stimulus, no neuronal cell death

Question 7

Identify mechanisms by which apoptosis induction and autophagy are connected

Answer 7

Many proteins (Bcl-2) that regulate apoptosis/ cell death also control autophagy
- create problems in interpreting results of therapeutic interventions designed to target these proteins 

Apoptotic proteases (caspases) can cleave essential autophagy regulatiors inactivating them and therefore blocking the process of autophagy

In some cases (stavation induced cell death) autophagy protects by providing essential nutrients in short term other times not as clare (chemo exposure)