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MCB L13-14

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Pregunta:

Autophagosome formation

Autor: Alex Rapai



Respuesta:

Start with the Pre-autophagosomal structure/phagosomal assembly site (PAS). Focus of autophagy-related (Atg) proteins on membrane ER in mammals. Hierarchical action of 15 Atgs and associated complexes form the autophagosome. Complexes: mTORC1, Atg1/Unc-51-Like kinase and Class III PI3K. TORC1 as an energy sensing receptor- supresses ULK1 (also called Atg) under nutrient rich conditions. TORC1 deactivation - ULK1/Atg1complex is activated and translocates to domain of ER.ULK1/Atg1 complex phosphorylates the class III PI3K complex. This regulation is also promoted Exo84-containing exocyst complex. Atg9 vesicle interacts – possibly for membrane stability. PI3K is synthesising PI3P (PI3P recruits and activates other proteins, DFCP1 – promotes omegasome, WIPIs – maturation of omegasome and IM). Under no stress – Beclin1 in ER membrane bound, and inhibited by Bcl2. In stress – Bcl2 phosphorylated and Beclin1 joins complex.


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