Initiation and development of autophagy is modulated by several autophagy-related (ATG) genes, which have been identified in yeast and human. Autophagy begins with the formation and maturation of the double-membraned autophagosomes which engulf and deliver cargoes to lysosomes for degradation. The assembling process of autophagosomes is mediated by a family of core ATG proteins, including two ubiquitin-like systems. First, inactive precursor MAP1LC3/LC3 is cleaved by protease ATG4B at the conserved C-terminal glycine residue. After a set of transfer and activation by ATG7, ATG3 and ATG12-ATG5-ATG16L1, the processed LC3 (LC3-I) finally conjugates with phosphatidylethanolamine (PE) at the exposed glycine site via a covalent bond. So far, lipidated LC3, called LC3-II, has become a biomarker of autophagy because of its characteristic of anchoring into the autophagosome membrane. Upon fusion with lysosomes, ATG4B can, in turn, deconjugate LC3-PE to release LC3-I to the cytoplasm for reuse. Hence, ATG4B serves as a priming and delipidation enzyme whose fine regulation is essential for autophagy process.

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