Compartment-specific dynamics and functions of autophagy in neurons

Abstract

Autophagy is a lysosomal degradation pathway that is critical to maintaining neuronal homeostasis and viability. Autophagy sequesters damaged and aged cellular components from the intracellular environment, and shuttles these diverse macromolecules to lysosomes for destruction. This active surveillance of the quality of the cytoplasm and organelles is essential in neurons to sustain their long-term functionality and viability. Indeed, defective autophagy is linked to neurodevelopmental abnormalities and neurodegeneration in mammals. Here, we review the mechanisms of autophagy in neurons and functional roles for autophagy in neuronal homeostasis. We focus on the compartment-specific dynamics of autophagy in neurons, and how autophagy might perform non-canonical functions critical for neurons. We suggest the existence of multiple populations of autophagosomes with compartment-specific functions important for neural activity and function. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 298-310, 2018.

Keywords: autophagy; axonal transport; homeostasis; neurodegeneration; neurons.

Figure 1. Diagram of the progression of autophagy

Cargoes are sequestered within double-membraned autophagosomes which then fuse with lysosomes for degradation. Autophagic cargo, as well as the inner membrane of the autophagosome, are degraded by resident lysosomal hydrolases. Degradation products (e.g. amino acids and lipids) can be re-used for new biosynthetic reactions.

Figure 2. Overview of compartment-specific autophagy in neurons

Key characteristics of autophagosome dynamics and function in the pre-synaptic terminal (A), mid-axon (B), soma (C), and dendrites (D). Blue arrows denote directionality of autophagosome movement.