Autophagosome formation: Where the secretory and autophagy pathways meet

Abstract

The upregulation of autophagosome formation in response to nutrient deprivation requires significant intracellular membrane rearrangements that are poorly understood. Recent findings have implicated COPII-coated vesicles, well known as ER-Golgi cargo transport carriers, as key players in macroautophagy. The role of COPII vesicles in macroautophagy and how they interact with autophagy-related (Atg) proteins was unknown. In our recent report, we show that during nutrient deprivation, phosphorylation of the membrane-distal surface of the COPII coat subunit Sec24 facilitates the interaction of Sec24 with the Atg machinery (specifically, Atg9) to regulate the abundance of autophagosomes during starvation. Phosphorylation of Sec24 is specifically required for macroautophagy, but not ER-Golgi transport. These findings begin to unravel the unique function of COPII vesicles during starvation-induced macroautophagy.

Keywords: COPII vesicles; autophagosome formation; autophagy and secretory pathway crosstalk; cell homeostasis; phosphorylation.

Figures

Figure 1.

Phosphorylation of Sec24 T324, T325 and T328 regulates autophagosome abundance in nutrient-deprived cells. Under nutrient-rich conditions, COPII vesicles bud from the ERES and transport secretory cargo to the Golgi (black arrows). During starvation (red arrows), autophagosome formation is initiated and Atg9 vesicles traffic from the late Golgi to the PAS. The membrane distal surface of Sec24 becomes phosphorylated, facilitating the interaction of Sec24 with the C terminus of Atg9. These events increase autophagosome number to rapidly make more nutrients for the starving cell.