Autophagosome Maturation: Regulating Two Successive Steps

Plenty of information is available about molecular mechanisms that underlie the first and last steps of macroautophagy, autophagosome (AP) formation and mature AP fusion with the lysosome, respectively. In contrast, not much is currently known about factors that regulate AP maturation. Mature APs are closed doublemembrane organelles that lack phosphatidylinositol-3phosphate (PI3P) and most of the Atg proteins; removal of both is required for AP fusion. In a recent paper, we showed that the yeast Rab5-like Vps21 GTPase module is important for AP closure. In addition, we showed that this step precedes that of PI3P and Atgs removal, for which the PI3P phosphatase Ymr1 is important. Mature APs then fuse with the lysosomal membrane in a Rab7/Ypt7dependent manner. Thus, we delineate two successive steps between AP expansion and fusion: Rab5-regulated AP closure and Ymr1-regulated PI3P and Atg removal. Notably, these three players, Rab5, Ymr1 and Ypt7, are known regulators of endocytosis.

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