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. 2018 Jul 26;9:1008. doi: 10.3389/fphys.2018.01008

FIGURE 1.

FIGURE 1

Molecular mechanisms describing the autophagy process that occur in the retinal pigment epithelium. Phosphatidylinositol-3-kinase-I (PI3K-I) is activated and this leads to the activation of the mechanistic target of Rapamycin (mTOR) triggering the dissociation of the serine/threonine-protein kinase complex (ULKc) that binds to the endoplasmic reticulum (ER). Subsequently, PI3K-III complex is activated and forms the phosphatidylinositol 3-phosphate (PI3P) pool in the rough ER. The Double FYVE-containing protein 1 (DFCP1) recognizes the new synthetized PI3P and forms the omegasome with the help of the ER. The WD repeat domain phosphoinositide-interacting protein 2 (WIPI-2) localizes to the omegasome-anchored phagophores. Then, Atg7 or E1 like (activation enzyme) together with Atg10 or E2 conjugation like enzyme activates the union of Atg5 and Atg12 (Atg5-Atg12) with Atg16. Atg7 also activates light chain 3-I (LC3-I) or Atg3, that forms LC3-II, also called Atg8 or LC3-phosphatidyl ethanolamine (LC3-PE). LC3-II gets inserted into the phagophore through the union to Atg5. Later on, P62 links ubiquitinated proteins or mitochondria to LC3 and the phagopore. Finally, the autophagosome formed, fuses with the lysosome to form the autolysosome.