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2017 ; 7
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Regulation of Autophagy through TORC1 and mTORC1
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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.
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