In vitro and in vivo reconstitution systems reveal the membrane remodeling ability of LC3B and ATG16L1 to form phagophore-like membrane cups.

Abstract

Macroautophagy/autophagy is a conserved pathway allowing the cell to clear and recycle unwanted materials. While decades of research have revealed molecular players and their hierarchical relationships in autophagy, the detailed mechanism by which these molecules function remains largely unknown. In a recent study, Jagan et al. revealed the membrane remodeling ability of two important proteins, MAP1LC3B/LC3B and ATG16L1, in autophagy. LC3B and the ATG12-ATG5-ATG16L1 complex function synergically to induce the formation of phagophore-like membrane cups on membranes both in vitro and in vivo. In addition, the authors showed that the recently characterized C-terminal membrane-binding domain of ATG16L1 is required for the cup formation and the subsequent transition to autophagic vesicles. Together this research provides more insight into the molecular function of LC3B and ATG16L1, as well as a possible mechanism for phagophore biogenesis.