Something more to read:

J Neurosci Res. 2019 Aug;97(8):897-913. doi: 10.1002/jnr.24411. Epub 2019 Mar 18.

Mechanisms for the maintenance and regulation of axonal energy supply.

Chamberlain KA¹, Sheng ZH¹.

Author information

1

The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.

Abstract

The unique polarization and high-energy demand of neurons necessitates specialized mechanisms to maintain energy homeostasis throughout the cell, particularly in the distal axon. Mitochondria play a key role in meeting axonal energy demand by generating adenosine triphosphate through oxidative phosphorylation. Recent evidence demonstrates how axonal mitochondrial trafficking and anchoring are coordinated to sense and respond to altered energy requirements. If and when these mechanisms are impacted in pathological conditions, such as injury and neurodegenerative disease, is an emerging research frontier. Recent evidence also suggests that axonal energy demand may be supplemented by local glial cells, including astrocytes and oligodendrocytes. In this review, we provide an updated discussion of how oxidative phosphorylation, aerobic glycolysis, and oligodendrocyte-derived metabolic support contribute to the maintenance of axonal energy homeostasis.

Cell Rep. 2019 Jul 2;28(1):51-64.e4. doi: 10.1016/j.celrep.2019.06.013.

Neuronal Soma-Derived Degradative Lysosomes Are Continuously Delivered to Distal Axons to Maintain Local Degradation Capacity.

Farfel-Becker T¹, Roney JC¹, Cheng XT¹, Li S¹, Cuddy SR¹, Sheng ZH².

Author information

1

Synaptic Function Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Room 2B-215, 35 Convent Drive, Bethesda, MD 20892-3706, USA.

2

Synaptic Function Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Room 2B-215, 35 Convent Drive, Bethesda, MD 20892-3706, USA. Electronic address: [email protected].

Abstract

Neurons face the challenge of maintaining cellular homeostasis through lysosomal degradation. While enzymatically active degradative lysosomes are enriched in the soma, their axonal trafficking and positioning and impact on axonal physiology remain elusive. Here, we characterized axon-targeted delivery of degradative lysosomes by applying fluorescent probes that selectively label active forms of lysosomal cathepsins D, B, L, and GCase. By time-lapse imaging of cortical neurons in microfluidic devices and standard dishes, we reveal that soma-derived degradative lysosomes rapidly influx into distal axons and target to autophagosomes and Parkinson disease-related α-synuclein cargos for local degradation. Impairing lysosome axonal delivery induces an aberrant accumulation of autophagosomes and α-synuclein cargos in distal axons. Our study demonstrates that the axon is an active compartment for local degradation and reveals fundamental aspects of axonal lysosomal delivery and maintenance. Our work establishes a foundation for investigations into axonal lysosome trafficking and functionality in neurodegenerative diseases.