1. Figure 2 Autophagosome formation in mammalian cells
Figure 2 | Autophagosome formation in mammalian cells. Induction of autophagy activates the serine/threonine- protein kinase ULK1 complex, which translocates to sites near the endoplasmic reticulum. The ULK1 complex in turn regulates the class III phosphatidylinositol 3-kinase (PI3K) complex. The multi-membrane spanning protein autophagy-related protein 9A (ATG9L) is involved in an early stage of autophagosome formation. Formation of phosphatidylinositol 3-phosphate (PI3P) recruits zinc finger FYVE domain-containing protein 1 (DFCP1) and promotes the formation of the omegasome. Other PI3P-binding WIPI (WD repeat domain phosphoinositide-interacting protein) family proteins, the ATG12–ATG5–ATG16L complex and the microtubule-associated proteins 1A/1B light chain (LC3)–phosphatidylethanolamine (PE) conjugate have important roles in the elongation and closure of the isolation membrane. LC3 is synthesized in a precursor form (pro-LC3) and cleaved at the C-terminus by ATG4B, becoming a mature form (LC3-I). LC3-I is conjugated to PE through ATG conjugating systems. LC3–PE is referred to as LC3-II. Fusion between the autophagosome and lysosome is mediated by the SNARE proteins syntaxin 17 (STX17), synaptosomal-associated protein 29 (SNAP-29) and vesicle-associated membrane protein 8 (VAMP8). ATG14, a component of the class III PI3K complex, facilitates this fusion event through direct binding to the STX17–SNAP-29 complex. Pleckstrin homology domain-containing family M member 1 (PLEKHM1), which can associate with Ras-related protein RAB7A, homotypic fusion and protein sorting complex (HOPS), and LC3, also accelerates membrane fusion. ER, endoplasmic reticulum; mLST8, target of rapamycin complex subunit LST8; RAPTOR, regulatory-associated protein of mTOR; VPS15, phosphatidylinositol 3-kinase regulatory subunit type 3; VPS34, phosphatidylinositol 3-kinase catalytic subunit type 3.
Ueno, T. & Komatsu, M. (2017) Autophagy in the liver: functions in health and disease
Nat. Rev. Gastroenterol. Hepatol. doi: /nrgastro