fig1

Figure 1. Schematic representation of autophagic flux. Autophagy starts with formation of phagophore (the initiation step), followed by the nucleation step where class III phosphatidylinositol 3-kinase (PI3K) complex, containing BECLIN-1, VPS34, and other molecules, elongates phagophore and encapsulates the cargo that should be degraded, result in formation of autophagosome. The next elongation step involves two ubiquitin like conjugation systems - the LC3-PE and ATG5-ATG12 systems. In the former, processed and lipidated LC3 (LC3-II) is recruited to the phagophore/autophagosome, as is p62, an adaptor molecule for selective autophagy of ubiquitinated proteins (Ub-p). The latter is essential for proper curvature of the phagosome. ATG7 is involved in both systems. The autophagosome then fuses with the lysosome to form autolysosome, in which the cargo is degraded by the lysosomal enzymes. mTOR negatively controls autophagic activity, whose activity is controlled positively by nutrients and negatively by rapamycin and other stress signals such as starvation. 3-MA inhibits autophagy at the early step of autophagic flux by inhibiting class III PI3K, and chloroquine at its late step by raising the lysosomal pH and then inhibiting the fusion between the autophagosome and the lysosome. LC3: light chain 3; CQ: chloroquine; 3-MA: 3-methyladenine