Autophagy Flashcards
3 types of autophagy
macroautophagy
Microautophagy
Chaperone-mediated autophagy
Chaperone-mediated autophagy
very complex and specific.
Involves recognition by hsc-70 complex (protein must have recognition site for this).
Gets chaperoned to lysosome.
Lysosomal hsc70 helps unfold and move it.
Diff b/c moves proteins 1 by 1 and is very selective.
Macroautophagy
Main pathway.
Eradicates damaged organelles/unused proteins.
Involves autophagosome.
Complex. Genetically programmed.
Longer lived proteins go to lysosome, shorter to proteosome.
Macroautophagy fx.
Recycle under deprivation, remove organelles, allow survival under stress, immunology, neuroprotection, remove intracell pathogens, aging, tumor suppression (beclin 1) or promotion
Atg genes
regulate autophagy. Therapy targets? But not exclusively involved in autophagy…
Autophagy process
1.) Induction (starvation, GF, chemo etc)
2.) Vesicle nucleation (phagophore, at ER, mito, PM)
3.) Cargo targeting (LC3II p62)
5.) Vesicle closure (Autophagosome)
6.) Vesicle fusion with endosome (amphisome), sometimes
7.) Vesicle fusion with lysosome (autolysosome)
permease, cells recycled
p62
cargo targeting. Recognizes LC3II and it recognizes ubiquinated proteins. drags to lysosome.
Autophagy regulation
Many things. Often feed into mTOR path.
Hypoxia/energy feed into mTOR.
Apoptosis regulates autophagy
Inhibits it.
Caspase cleaved off beclin amplifies apoptosis. Turns of autophagy.
Caspase also regulate autophagosomes.
Beclin 1
Part of complex. Contains BH3 domain, interacts with BCL-2 and BCL-1 (regulate apopotosis)
BH3 competes off Bcl2 for beclin1, which would induce autophagy.
If you stop BH3/Bcl2 interaction get autophagy. hard to tell if you are affecting apoptosis or autophagy.
Neurodegeneration
Aggregate proteins cause neuron death, autophagy degrades aggregates. Delay onset of disease?
