Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function.

ATG5 is one of the core autophagy proteins with additional functions such as noncanonical membrane atg8ylation, which among a growing number of biological outputs includes control of tuberculosis in animal models. Here, we show that ATG5 associates with retromer's core components VPS26, VPS29, and VPS35 and modulates retromer function. Knockout of ATG5 blocked trafficking of a key glucose transporter sorted by the retromer, GLUT1, to the plasma membrane.

ATG9A facilitates the closure of mammalian autophagosomes.

Canonical autophagy captures within specialized double-membrane organelles, termed autophagosomes, an array of cytoplasmic components destined for lysosomal degradation. An autophagosome is completed when the growing phagophore undergoes ESCRT-dependent membrane closure, a prerequisite for its subsequent fusion with endolysosomal organelles and degradation of the sequestered cargo. ATG9A, a key integral membrane protein of the autophagy pathway, is best known for its role in the formation and expansion of phagophores.

Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function.

ATG5 is one of the core autophagy proteins with additional functions such as noncanonical membrane atg8ylation, which among a growing number of biological outputs includes control of tuberculosis in animal models. Here we show that ATG5 associates with retromer's core components VPS26, VPS29 and VPS35 and modulates retromer function. Knockout of ATG5 blocked trafficking of a key glucose transporter sorted by the retromer, GLUT1, to the plasma membrane.

Membrane atg8ylation in Canonical and Noncanonical Autophagy.

Membrane atg8ylation is a homeostatic process responding to membrane remodeling and stress signals. Membranes are atg8ylated by mammalian ATG8 ubiquitin-like proteins through a ubiquitylation-like cascade. A model has recently been put forward which posits that atg8ylation of membranes is conceptually equivalent to ubiquitylation of proteins.