FIGURE 2.

The mTORC2‐AKT‐SGK axis in autophagy. mTORC2 phosphorylates Ser473 of AKT, whereas GSK3b prevents this through an inhibitory phosphorylation of RICTOR. In turn, the phosphatase PHLPP1 can remove the phosphorylation of Ser473 in AKT. pAKT at Ser473 can place inhibitory phosphorylations on Ser234/Ser295 of Beclin‐1 and Ser253/Thr32 of FoxO3, which interferes with the role of these two proteins in the positive modulation of autophagy. pAKT at Ser473 also phosphorylates and inhibits GFAP, resulting in negative regulation of LAMP2A‐mediated CMA. mTORC2 phosphorylates Ser422 of SGK‐1 which, in turn, phosphorylates Thr32 of FoxO3 and Ser104 of VDAC1. pFoxO3 does not participate in the transcriptional upregulation of autophagy and it is believed to reduce the expression of ULK1 and further inhibit autophagy. SGK‐1‐mediated inhibitory phosphorylation of VDAC1 reduces autophagy, mitophagy, and associated mitochondrial permeability