The Role of Lipids in the Control of Autophagy

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, as well as on the lipidation of Atg8/LC3-like proteins, this area of research has recently expanded, implicating a variety of other lipids, such as phosphatidic acid and diacylglycerol, and their metabolizing enzymes in macroautophagy. This review summarizes this progress and highlights the role of specific lipids in the various steps of macroautophagy, including the signaling processes underlying macroautophagy initiation, autophagosome biogenesis and maturation.