Autophagy is traditionally depicted as a signaling cascade that culminates in the formation of an autophagosome that degrades cellular cargo. However, recent studies have identified myriad pathways and cellular organelles underlying the autophagy process, be it as signaling platforms or through the contribution of proteins and lipids. The Golgi complex is recognized as being a central transport hub in the cell, with a critical role in endocytic trafficking and endoplasmic reticulum (ER) to plasma membrane (PM) transport. However, the Golgi is also an important site of key autophagy regulators, including the protein autophagy-related (ATG)-9A and the lipid, phosphatidylinositol-4-phosphate [PI(4)P]. In this review, we highlight the central function of this organelle in autophagy as a transport hub supplying various components of autophagosome formation. Basic Mechanisms of AutophagyAutophagy is a process whereby cellular material is degraded to procure nutrients or to remove organelles and proteins [1]. This highly conserved, essential process is mediated by a cohort of proteins called the ATG proteins, which are conserved from yeast to humans. There are many different cues that initiate autophagy, but perhaps the best known is amino acid starvation, which induces autophagy to offset the lack of nutrients. Autophagy can be seen as a complex pathway of membrane formation and reformation, centered on the de novo creation of a double-membraned autophagosome, which will fuse with the lysosome so as to degrade its cargo [1].Many aspects of autophagosome formation are by now well understood and, in simplified form, can be viewed as a cascade starting from the mammalian target of rapamycin (mTOR), which activates the Unc-51-like kinase 1 (ULK1) complex, followed by phosphatidylinositol 3-phosphate [PI(3)P] generation at the ER by the phosphatidylinositol 3-kinase catalytic subunit type 3 [PI(3) KC3] complex I. The generation of PI(3)P at the ER leads to the recruitment of autophagy effectors to form the omegasome, the earliest autophagic structure, which grows into the phagophore. One of the effectors that bind PI(3)P is WIPI2B, which has an important role in the lipidation and membrane association of LC3/GABARAPs (e.g., LC3-II; see Glossary), which are essential for autophagy and are the most widely used markers of autophagosomes. Once the phagophore has grown and enclosed its cargo, it closes to form an autophagosome [1,2].An important player in each step of this process is ATG9A, a transmembrane protein that cycles between the trans-Golgi network (TGN) and the ATG9 compartment [3]. Curiously, although essential at all stages for autophagosome formation, ATG9A does not have a defined function as far as we know [2]. Thus, many questions remain about autophagosomal membrane formation and the role of ATG9A. In particular, because it is the only transmembrane core autophagy protein, could ATG9A contribute lipids to help form the autophagosome? In addition, which proteins or lipid species could be trafficked by ATG9A to the...
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