Skip to main content
. 2019 Jun;14(6):954–961. doi: 10.4103/1673-5374.250569

Figure 1.

Figure 1

Process and molecular mechanisms of autophagy in cerebral ischemia/reperfusion injury (CIRI).

The process of macroautophagy goes through initiation, vesicle nucleation, expansion and maturation of autophagosomes, and fusion and degradation of autophagolysosomes. Cerebral ischemia/reperfusion leads to a lower level of ATP and activates AMPK, which further inhibits mTORC1 and activates the ULK1-Atg 13-focal adhesion kinase FIP200 complex, thus initiating autophagy. The ULK1-Atg13-FIP200 complex phosphorylates Beclin-1 and activates the class-III PI3K complex, promoting the formation of vesicles with double-layer membranes. The double-membrane further bends and extends to form mature autophagosomes, a process that requires the Atg12-Atg5-Atg16L1 complex and the LC3-PE conjugate. The fusion of autophagosomes and lysosomes is mediated by SNAREs, small GTPase Rab7, and other proteins. Finally, the autophagolysosomes are degraded by lysosomal enzymes, which requires p62-mediated degradation of cargoes. ATP: Adenosine triphosphate; AMPK: adenosine monophosphate-activated protein kinase; mTORC1: mammalian target of rapamycin complex 1; ULK1: UNC-51-like kinase-1; Atg: autophagy-related-gene; FIP200: family-interacting protein of 200 kDa; PI3K: phosphatidylinositol 3-kinase; LC3: microtubule associated protein-1 light chain 3; PE: phosphatidylethanolamine; UVRAG: UV radiation resistance-associated gene; SNARE: soluble N-ethylmaleimide sensitive factor attachment protein receptors.