Autophagy Flashcards
Macroatophagy
bulk degradation of cellular components through vesicle budding and fusion with lysosome
Chaperone-mediated Autophagy
Recognition of KFERQ motif by numerous proteins followed by delivery to lysosome
Macroatophagy Process
Induced by nutrient starvation, GF mediated starvation, chemo exposure, Rapamycin, etc.
Regulated by Atg proteins
Vesicle formation stimulated by mTOR signaling and ULK1 kinase activity.
Vesicle nucleation creates phagophore, Vesicle expansion creates Omegasome; Cargo targeting by LC3II and p62; vesicle closure into autophagosome; vesicle fuses with endosome and then lysosome.
Beclin-1
Atg protein, acts as scaffold
Autophagy and neuroprotection
Autophagy can remove protein aggregates, might be protective against aggregating protein diseases
Apoptosis-Autophagy Connection
Beclin-1 is scaffold Atg protein in autophagy but amplifies apoptosis signal after caspase cleavage.
Beclin-1 forms complex with Bcl2 via its BH3 domain which binds Bcl2. This prevents autophagy.
BH3 protein production causes Beclin-1 dissociation and causes authophagy.
Autophagy protective or apoptotic?
We see both. Some types of cell death appear to by Atg dependent.
Other times, increased autophagy seems to increase cell survival