ATG8

ATG8 is a ubiquitin-like protein that plays a central role in macroautophagy across eukaryotes. It was identified in the budding yeast Saccharomyces cerevisiae as essential for autophagosome formation and remains a core component of the autophagic machinery in many organisms. In yeast, ATG8 is required for the expansion of the isolation membrane and recruitment of cargo receptors.

ATG8 is synthesized as a proprotein and is processed by the cysteine protease ATG4 to reveal a C-terminal glycine. The processed Atg8 is then conjugated to the lipid phosphatidylethanolamine (PE) through a ubiquitin-like conjugation system involving the E1-like enzyme ATG7 and the E2-like enzyme ATG3, producing Atg8-PE. This lipidation anchors Atg8 to autophagosomal membranes and promotes membrane expansion and autophagosome maturation. Atg8-PE also serves as a docking site for cargo receptors and adapters that contain LC3-interacting region (LIR) motifs, facilitating selective autophagy.

In mammals, Atg8 homologs are grouped into the LC3 and GABARAP families, with LC3A, LC3B, LC3C and GABARAP proteins performing related roles. The conversion of LC3-I to LC3-II (the lipidated form) is commonly used as a biochemical readout of autophagy flux in cells.

ATG8/LC3 proteins are highly conserved and widely used as molecular markers for autophagosomes in cellular studies. They participate in multiple forms of autophagy, including nonselective and selective pathways, and interact with cargo adaptors to mediate degradation of specific substrates.