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. 2019 Apr 8;43:632–640. doi: 10.1016/j.ebiom.2019.04.005

Fig. 1.

Fig. 1

(a) Under conditions of reduced levels of leucine or arginine as a result of a LPD or a LPHC diet, Sestrin-2 or CASTOR1 interacts with and inhibits GATOR2, which is a positive regulator of mTORC1, leading to the suppression of mTORC1 activation. The suppression of mTORC1 is associated with the induction of autophagy and improvement of insulin resistance, resulting in longevity and metabolic health. (b) Leucine or arginine binds Sestrin-2 or CASTOR1 and induces their dissociation from GATOR2. GATOR2 contributes to mTORC1 activation, leading to the suppression of autophagy and induction of insulin resistance. (c) An increased level of SAM due to a reduction in Gnmt activity leads to mTORC1 activation through two pathways. LCMT1 activation by SAM induces increased levels of metylated-PP2A. Metylated-PP2A dephosphorylates p-Npr2 (a negative regulator of mTOR), resulting in mTORC1 activation. SAM binds SAMTOR and induces its dissociation from GATOR1. GATOR1 contributes to mTORC1 activation, leading to the suppression of autophagy and induction of insulin resistance. (d) MetR or Gnmt activation leads to the suppression of mTORC1 via reduced levels of SAM.