An in vitro compartmental system underlines the contribution of mitochondrial immobility to the ATP supply in the NMJ

• DOI: 10.1242/jcs.234492
• Publication Date: 2019-11-13T16:25:13Z
• Authors: Topaz Altman; Danielle Geller; Elisabeth Kleeblatt; Tal Gradus-Perry; Eran Perlson
• Keywords: Male; Motor Neurons; 0301 basic medicine; 0303 health sciences; Amyotrophic Lateral Sclerosis; Neuromuscular Junction; Fluorescent Antibody Technique; Axons; Coculture Techniques; Mitochondria; Mice; 03 medical and health sciences; Adenosine Triphosphate; Microscopy, Fluorescence; Animals; Humans; Female; Myocytes, Cardiac; Muscle, Skeletal; Plasmids

The neuromuscular junction (NMJ) is the largest, most-complex synapse in human body. Motor neuron (MN) diseases, such as amyotrophic lateral sclerosis (ALS), specifically target MNs and NMJs. However, little known about reasons for MN-selective neuronal synaptic vulnerability MN diseases. Here, utilizing a compartmental microfluidic vitro co-culture system, we provide possible explanation why NMJ, other than its unusual dimensions, differs from synapses. By using live-imaging techniques, discovered that cultured display higher axonal mitochondrial immobility compared with sympathetic neurons (SNs), leading to profound enrichment of mitochondria only NMJ. Furthermore, by employing ATP sensor, show respiration key contributor production NMJs but not SN Taken together, our data suggest localization underlies unique specific qualities Our findings shed light on role NMJ maintenance, possibly indicate how may serve source selective neurodegenerative diseases.This article has an associated First Person interview first author paper.