Fig. 1

The mechanisms behind SIRT3-regulated autophagy. SIRT3 deacetylates Foxo1 and Foxo3a to first activate the E3 ligases Pink1 and Parkin, thereby initiating the activation of autophagy and mitochondrial autophagy. Subsequently, SIRT3 activates LKB1 and phosphorylates AMPK and PI3K. The phosphorylation of AMPK directly inhibits mTOR and the phosphorylation of PI3K promotes AKT phosphorylation thus further inhibiting mTOR. The inhibition of mTOR promotes autophagy. In addition, SIRT3 can significantly enhance the SOD2 function by promoting its antioxidant activity and deacetylation of its key lysine residues thus eventually leading to a reduction in the cellular ROS levels and the inhibition of autophagy