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.
Highlights
In 2016, the Nobel Prize for physiology and medicine was awarded to Dr Yoshinori Ohsumi for the discovery of the mechanism of autophagy
The Ohsumi lab, along with the Klionsky and Thumm labs, identified a group of autophagy-related genes (Atg), which encoded proteins that were mostly involved in autophagy membrane biogenesis in yeast [3,4,5]
The short answer is that target of rapamycin complex 1 (TORC1) coordinates them
Summary
In 2016, the Nobel Prize for physiology and medicine was awarded to Dr Yoshinori Ohsumi for the discovery of the mechanism of autophagy. The direct substrate of TORC1 in yeast is Atg, which is hyper-phosphorylated under is still unknown, but two forms of protein phosphatase 2A (PP2A), PP2A–Cdc and PP2A–Rts, nutrient-rich conditions (Figure 1) [9,10,11]. Phosphorylation in the MIM domain weakens this interaction; as in the case of Atg, the Atg13–Atg interaction is facilitated by starvation has another region called the MIM domain, which binds the protein kinase in a TORC1-dependent regulation manner (Figure 1) [10,14]. Atg kinase activity is upregulated and autophagy is induced [10] This regulation is conducted by self-association of different Atg molecules and auto-phosphorylation [19]. The involvement of TORC1-dependent processes in these later stages is scarcely known (except for the expression control of Atg described below), and will be described in detail elsewhere [39,40]
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