The autophagosome: origins unknown, biogenesis complex

Autophagy is an evolutionarily conserved lysosome-mediated degradation process that involves membrane-bound organelles called autophagosomes. Macroautophagy, commonly referred to as autophagy, is induced by amino acid starvation.Autophagosome formation is mediated by autophagy-related (ATG) proteins. There are more than 34 ATG proteins in yeast, of which almost half are conserved in mammals.Amino acid starvation inactivates mammalian target of rapamycin complex 1 (mTORC1), which leads to the induction of autophagy and increased autophagsome formation. Both the UNC51-like kinase (ULK) complex and the autophagy-specific class III PI3K complex are activated downstream of mTORC1 inactivation.Autophagosome formation after amino acid starvation occurs at contact sites between the endoplasmic reticulum (ER) and mitochondria. Expansion of the site occurs on omegasomes, which are platforms that are enriched in phosphatidylinositol 3-phosphate produced by the autophagy-specific PI3K complex.Omegasomes give rise to isolation membranes (also known as phagophores), which recruit ATG proteins, including the ULK complex, the PI3K complex, WD-repeat domain phosphoinositide-interacting 2 (WIPI2), ATG12, ATG5, ATG16L1 and LC3.Expansion of the isolation membrane is driven by vesicular traffic from several cellular compartments, including the ER–Golgi intermediate compartment (ERGIC), the Golgi and recycling endosomes. Expansion of the isolation membrane is followed by detachment from the omegasome and closure of the vesicle around the cytosolic proteins and membranes.