Figure 5.

Mechanism of natural compounds or small molecules to activate mTOR and TFEB in autophagy–lysosomal process. Natural compounds or small molecules inactivate AKT and mTOR, which promote the accumulation of TFEB in the cytoplasmic and its nuclear translocation. TFEB in cytoplasm is heavily phosphorylated and interacts with mTOR in the lysosome surface. The inactivation of mTOR activity stimulates the dephosphorylation of TFEB. Subsequently, dephosphorylated TFEB is translocated from cytoplasm to nucleus. In nucleus, TFEB binds to the promoter regions of autophagy- and lysosomal-associated genes and induces gene expression in addition to lysosome biogenesis. The aggresome is bound to the phagophore, resulting in the formation of the autophagosome. Eventually, the autophagosome fused with lysosome degrades aggresomes via aggrephagy process.