Fig. 3
From: ROS signaling under metabolic stress: cross-talk between AMPK and AKT pathway
Signaling of AMPK and AKT on the ROS homeostasis via mTOR and FOXO regulation: Under metabolic stress, AMPK inhibits mTOR mainly via two ways:phosphorylates TSC2 at Ser-1387 which stimulates the TSC1-TSC2 complex to inhibit Rheb’s ability to activate mTOR; phosphorylates Raptor at Ser-792/Ser-722 to inhibit mTOR1. AKT activates mTOR reversely: AKT phosphorylates TSC2 at another site and activates mTOR via Rheb; AKT phosphorylates PRAS40 to inhibit its ability to suppress mTOR. Activated mTOR in turn promotes protein synthesis through S6K1 and 4E-BP1. AMPK phosphorylates FOXO, promoting the translocation to nucleus. AMPK also facilitates FOXO acetylation and enhances its transcriptional activity of antioxidant genes: SOD, Catalase, Sestrin. Additionally, AMPK promotes NADPH production via the PPP. On the other hand, AKT phosphorylates FOXO and leads to the translocation from the nucleus to the cytoplasm. By ubiquitination of FOXO, AKT leads to its degradation in cytoplasm