Fig. 3: Activation and localization of the ATG8 conjugation machinery in macroautophagy.

Schematic representation of the cascade that leads to ATG8 lipidation on the target membrane. In yeast and mammals PI3KC3-C1 activity is necessary to produce PI3P and to recruit PI3P-sensor proteins (Atg21 or WIPIs) to the pre-autophagosomal membrane. These proteins in turn bind the E3-like ligase via the ATG16 subunit and thereby recruit and activate the E3-like ligase activity. Correct membrane localization of the lipidation reaction is also mediated by the E2-like ATG3 that directly interacts with the ATG12 subunit of the E3 and its N-terminal amphipathic helix that inserts into the lipid bilayer (shown as black line). In yeast, ATG5 was shown to directly interact with poorly packed membranes, while in mammals ATG16L1 binds the membrane. Legend: the ATG8 protein family members are shown in green and the PI3P lipid is shown in blue.