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Macroautophagy is an essential cellular pathway mediating the lysosomal degradation of defective organelles, long-lived proteins and a variety of protein aggregates. Similar to other intracellular trafficking pathways, macroautophagy involves a complex sequence of membrane remodeling and trafficking events. These include the biogenesis of autophagosomes, which engulf portions of cytoplasm at specific subcellular locations, and their subsequent maturation into autophagolysosomes through fusion with the endo-lysosomal compartment. Although the formation and maturation of autophagosomes are controlled by molecular reactions occurring at the membrane–cytosol interface, little is known about the role of lipids and their metabolizing enzymes in this process. Historically dominated by studies on class III phosphatidylinositol 3-kinase (also known as Vps34) and its product phosphatidylinositol-3-phosphate …