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Molecules to Medicine III > Autophagy > Flashcards

Flashcards in Autophagy Deck (7)
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1

What are the types of autophagy?

macrophagy, chaperone-mediated autophagy (2 most important)
and microautophagy

2

Name at least 5 functions of (macro)autophagy

- 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

3

What are the steps of the autophagic process?

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)

4

Describe macrophagy

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

5

Describe chaperone mediated autophagy

recognition of protein containing KFERQ aa motif
- direct binding and delivery to lysosome

6

Describe the rationale behind autophagy's protective action against neurodegeneration

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

7

Identify mechanisms by which apoptosis induction and autophagy are connected

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)