Fig. 2

Diagram illustrates the positions of Sal’s inhibition of autophagic flux. Macroautophagy begins with engulfment of the cytoplasmic materials by the phagophore, which detains the materials into a double-membrane vesicle (i.e. autophagosome). The autophagosome fuses with a lysosome to form an autolysosome, and then the contents are degraded by the lysosome. Initiation of autophagosome formation requires the ULK1-Atg13-FIP200 complexes and Beclin1-class III PI3K complexes. Two conjugation systems, Atg12-Atg5-Atg16 and LC3, are critical to the elongation and enclosure step of the autophagosome formation. Lipid conjugation leads to the conversion of the soluble form of LC3-I to the autophagic vesicle-associated form LC3-II, which is widely used as a marker of autophagy. Sal is found to increase the lysosome membrane permeability (LMP), which affects the acidification and the integrity of lysosomes. Moreover, Sal can also inactivate cathepsins in lysosomes, resulting in the inhibition of lysosomal activity