The Role of Autophagy in the Pathogenesis of Diabetic Nephropathy
Figure 2
Autophagy regulation. (a) ULK1 protein kinase complex. ULK1 is a critical regulator of nutrient-related autophagy. mTOR-dependent phosphorylation of ULK1 (Atg1) and Atg13 under nutrient-rich conditions inhibits autophagy. In contrast, AMPK-dependent phosphorylation of ULK1 activates autophagy induction under energy-depleted condition. (b) PI3K complex. Phosphatidylinositol 3-kinase (PI3K) phosphorylates phosphatidylinositol in the membrane lipid to create phosphatidylinositol 3-phosphate. Class III PI3K comprises hVps34, hVps15, Beclin-1, and Atg14. (c) Atg12-Atg5-Atg16 complex and LC3-II. Unlike other ubiquitin-like proteins, the ubiquitin-like protein Atg12 has a C-terminal glycine, which protects it from processing. Atg12 is conjugated to the substrate Atg5 by Atg7 and Atg10. The Atg12-Atg5 conjugate forms a complex with Atg16. Self-oligomerization of Atg16 results in a multimer of the Atg12-Atg5-Atg16 complex. After the ubiquitin-like protein LC3 has had its C-terminal arginine residue cleaved by the cysteine protease Atg4, it is passed on to Atg7 and Atg3 and transferred into the head group of its substrate phosphatidylethanolamine (PE). This LC3-PE conjugate functions as part of the membrane component of the autophagosome. When LC3-PE is once again deconjugated to PE by Atg4, Atg8 is recycled.
