Atg8ylation

[2] Together, they comprise a sub-class of ubiquitin-like molecules characterized by two N-terminal α-helices added to the ubiquitin core, which serve a dual role of forming a docking site for interacting proteins containing ATG8-interaction motifs and enhancing mATG8’s affinity for membranes.

[4] The conjugation cascade that activates mATG8s and results in membrane atg8ylation is biochemically similar to protein ubiquitylation, as both systems require ATP, E1, E2 and E3 ligases.

[3] Mammalian membranes that undergo atg8ylation include: canonical autophagosomes, phagosomes harboring phagocytosed pathogens or microbial products, perturbed or signaling endosomes, damaged lysosomes, exocytic compartments releasing exosomes, endoplasmic reticulum (ER) during its piecemeal ESCRT-dependent lysosomal degradation, and lipid droplets.

During canonical autophagy, which includes atg8ylation of growing phagophores, WIPI2, an effector of phosphatidylinositol-3-phosphate (a stress-signaling phosphoinositide phospholipid) and a known interactor of ATG16L1 , helps dock the E3 ligase ATG12-ATG5/ATG16L1 to the phosphatidylinositol-3-phosphate-marked membranes.

[15] The non-autophagic processes dependent on atg8ylation include: LAP (LC3-associated phagocytosis), LANDO (LC3-associated endocytosis), LC3-associated micropinocytosis (LAM), CASM (conjugation of ATG8 to single membranes) alternatively referred to as SMAC (single membrane ATG8 conjugation) , and ‘vATPase-ATG16L1 axis xenophagy’ known under an acronym VAIL (V-ATPase-ATG16L1-induced LC3 lipidation).