Membrane Trafficking in Autophagy

Macroautophagy is an intracellular pathway used for targeting of cellular components to the lysosome for their degradation and involves sequestration of cytoplasmic material into autophagosomes formed from a double membrane structure called the phagophore. The nucleation and elongation of the phagophore is tightly regulated by several autophagy-related (ATG) proteins, but also involves vesicular trafficking from different subcellular compartments to the forming autophagosome. Such trafficking must be tightly regulated by various intra- and extracellular signals to respond to different cellular stressors and metabolic states, as well as the nature of the cargo to become degraded. We are only starting to understand the interconnections between different membrane trafficking pathways and macroautophagy. This review will focus on the membrane trafficking machinery found to be involved in delivery of membrane, lipids, and proteins to the forming autophagosome and in the subsequent autophagosome fusion with endolysosomal membranes. The role of RAB proteins and their regulators, as well as coat proteins, vesicle tethers, and SNARE proteins in autophagosome biogenesis and maturation will be discussed.