Cells draw on a reservoir of tubules and vesicles to start building the membranes required for autophagy, Mari et al. say.
During autophagy, cells form a double-membraned autophagosome to engulf cytoplasmic components and deliver them to the lysosome for degradation. In yeast, autophagosome biogenesis begins at the phagophore assembly site (PAS), a region near the vacuole (the yeast equivalent of lysosomes) where autophagy proteins and lipid bilayers build the phagophore, a membranous sac that expands into a mature autophagosome. Where the PAS membranes come from is unknown. Mari et al. investigated their origin by tracing the movements of Atg9—the only conserved transmembrane autophagy protein and one of the first parts of the machinery to arrive at the PAS.
The researchers found that, before moving to the PAS, Atg9 localized to small clusters of tubules and vesicles that were often next to mitochondria. At the beginning of autophagy, one or more of these clusters moved en bloc toward the vacuole, where they formed the PAS. But where do these Atg9-containing tubules and vesicles come from in the first place? The transport of newly synthesized Atg9 was blocked by mutants preventing traffic through the secretory pathway, suggesting that these “Atg9 reservoirs” arise from the ER and/or the Golgi. Mari et al. think that the reservoirs can rapidly provide a cell with the membranes it needs to initiate autophagy in times of stress.
Senior author Fulvio Reggiori now wants to investigate which other proteins are stored in these unique compartments, and why they tend to wait near mitochondria. BS