Figure 4.

mTORC1 inhibits various steps of autophagy. mTORC1 phosphorylates and inhibits ULK1 and Atg13 which are part of the ULK complex, thereby blocking autophagy initiation step. mTORC1-mediated phosphorylation of Atg14, AMBRA1, and NRBF2 from the PI3KC3 complex I, which is one of the PI3KC3 complexes, negatively regulates autophagosomal nucleation step. mTORC1 also affects maturation of autophagosome through inhibitory phosphorylation of UVRAG. TFEB and TFE3 are transcription factors critical for lysosomal biogenesis and expression of autophagy genes. Different steps in the autophagy process are illustrated and denoted in blue. Bold letters in different complexes denote proteins that are phosphorylated by mTORC1.