The Journey of the Synaptic Autophagosome: A Cell Biological Perspective

Autophagy is a key cellular degradative pathway, important for neuronal homeostasis and function. Disruption of autophagy is associated with neuronal dysfunction and neurodegeneration. Autophagy is compartmentalized in neurons, with specific stages of the pathway occurring in distinct subcellular compartments. Coordination of these stages drives progression of autophagy and enables clearance of substrates. Yet, we are only now learning how these distributed processes are integrated across the neuron. In this review, we focus on the cell biological course of autophagy in neurons, from biogenesis at the synapse to degradation in the soma. We describe how the steps of autophagy are distributed across neuronal subcellular compartments, how local machinery regulates autophagy, and the impact of coordinated regulation on neuronal physiology and disease. We also discuss how recent advances in our understanding of neuronal autophagic mechanisms have reframed how we think about the role of local regulation of autophagy in all tissues.