Multiplexed suppression of TOR complex 1 induces autophagy during starvation

Figures & data

Figure 1. TORC1 regulation by GATOR1, the TSC complex, and Gcn2 in fission yeast. (A) The Gtr1-Gtr2 heterodimer is anchored to the vacuole by the Ragulator complex. Sea3 functions as part of GATOR1 to promote the GAP activity of GATOR1 toward the Gtr1 GTPase. Sea3 also mediates the association between GATOR1 and GATOR2 in the assembly of the GATOR holocomplex. (B) In response to amino acid starvation, Gcn2 suppresses TORC1 activity, whereas nitrogen starvation does not induce robust Gcn2 activation (a thinner arrow). Upon nitrogen starvation, the Sea3-GATOR1 complex primarily attenuates TORC1, with less contribution of the TSC complex (Tsc1-Tsc2), inducing autophagy that supplies enough amino acids to restrain Gcn2 activation. Cells deficient in GATOR1 and the TSC complex fail to induce autophagy, resulting in a cellular amino acid shortage that triggers the Gcn2-mediated TORC1 suppression