Journal of Molecular Biology

Overview of the autophagy machinery.

The role of WIPI proteins in autophagy.

The role of ATG16L1 in autophagy.

Molecular mechanisms of WIPI2 and ATG16L1 in selective and nonselective autophagy.

Autophagy is a conserved cellular recycling pathway that delivers damaged or superfluous cytoplasmic material to lysosomes for degradation. In response to cytotoxic stress or starvation, autophagy can also sequester bulk cytoplasm and deliver it to lysosomes to regenerate building blocks. In macroautophagy, a membrane cisterna termed phagophore that encloses autophagic cargo is generated. The formation of the phagophore depends on a conserved machinery of autophagy related proteins. The phosphatidylinositol(3)-phosphate binding protein WIPI2 facilitates the transition from phagophore initiation to phagophore expansion by recruiting the ATG12-ATG5-ATG16L1 complex to phagophores. This complex functions as an E3-ligase to conjugate ubiquitin-like ATG8 proteins to phagophore membranes, which promotes tethering of cargo to phagophore membranes, phagophore expansion, maturation and the fusion of autophagosomes with lysosomes. ATG16L1 also has important functions independently of ATG12-ATG5 in autophagy and beyond. In this review, we will summarize the functions of WIPI2 and ATG16L1 in selective and nonselective autophagy.

autophagy

WIPI2

E3-ligase

ATG12-ATG5-ATG16L1

ATG8 proteins

© 2025 The Author(s). Published by Elsevier Ltd.