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

Abstract:

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

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Altman T,Geller D,Kleeblatt E,Gradus-Perry T,Perlson E

doi

10.1242/jcs.234492

subject

Has Abstract

pub_date

2019-12-02 00:00:00

issue

23

eissn

0021-9533

issn

1477-9137

pii

jcs.234492

journal_volume

132

pub_type

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