Regulation of autophagy through TORC1 and mTORC1

Abstract

Autophagy is an intracellular protein-degradation process that is conserved across eukaryotes including yeast and humans. Under nutrient starvation conditions, intracellular proteins are transported to lysosomes and vacuoles via membranous structures known as autophagosomes, and are degraded. The various steps of autophagy are regulated by the target of rapamycin complex 1 (TORC1/mTORC1). In this review, a history of this regulation and recent advances in such regulation both in yeast and mammals will be discussed. Recently, the mechanism of autophagy initiation in yeast has been deduced. The autophagy-related gene 13 (Atg13) and the unc-51 like autophagy activating kinase 1 (Ulk1) are the most crucial substrates of TORC1 in autophagy, and by its dephosphorylation, autophagosome formation is initiated. Phosphorylation/dephosphorylation of Atg13 is regulated spatially inside the cell. Another TORC1-dependent regulation lies in the expression of autophagy genes and vacuolar/lysosomal hydrolases. Several transcriptional and post-transcriptional regulations are controlled by TORC1, which affects autophagy activity in yeast and mammals.