Dual suppressive effect of MTORC1 on autophagy: tame the dragon by shackling both the head and the tail.

The lysosome is a key subcellular organelle that receives and degrades macromolecules from endocytic, secretory and autophagic pathways. Lysosomal function is thus critical for an efficient autophagic process. However, the molecular mechanisms mediating lysosomal function upon autophagic induction are largely unknown. Our laboratory recently discovered that upon autophagy activation, the lysosome is activated, and this functional activation is dependent on MTORC1 suppression, suggesting that MTORC1 exerts a suppressive effect on lysosomal function. Therefore, data from our study demonstrate that MTORC1 exerts a dual inhibitory effect on autophagy, blocking autophagy not only at the initiation stage via suppression of the ULK1 complex, but also at the degradation stage via inhibition of lysosomal function. We think that understanding the negative regulatory effect of MTORC1 on lysosomal function expands the functional scope of MTORC1 in autophagy regulation, and offers new clues for developing novel interventional strategies in autophagy- and lysosome-related diseases.