Fig. 1.

The mechanism of mTOR associated with ferroptosis. Fe(III) is taken up by TFR, converted into Fe(II) by STEAP3 in the endosome, and finally stored in FT. Under the condition of low energy, AMPK is activated, which activates BECN1 and ULK1 and inhibits mTORC1 to promote cellular autophagy. BECN1 activation inhibits System Xc- and reduces GSH synthesis, which leads to increased PuFA-OOH and promotes ferroptosis. Upon cellular autophagy as well as intracellular Fe exhaustion, lysosomes bind to FT releasing large amounts of Fe(II) thereby resulting in the Fenton reaction leading to an increase in Lipid ROS, leading to ferroptosis. PI3K/AKT activation of mTORC1, mTOR downstream SREBP1 and SCD1 activation converts SFA into MuFAs, and P70S6K activation ultimately inhibits ferroptosis and autophagy. TFR, transferrin receptor; Lipid ROS, lipid reactive oxygen species; PUFA, poly-unsaturated fatty acid; MUFA, monounsaturated fatty acid; NRF2, nuclear factor erythroid 2-related factor 2; NOCA4, nuclear receptor coactivator 4; GPX4, glutathione peroxidase 4; GSH, glutathione; GSSH, oxidized glutathione; FTH, ferritin heavy chain; SREBP, sterol responsive element binding protein; ULK1, unc-51 like autophagy activating kinase 1; AMPK, AMP-activated protein kinase; BECN1, beclin 1; mTORC1, mechanistic target of rapamycin complex 1; (By Figdraw)