Open AccessIn vitro compartmental system underlines the contribution of mitochondrial immobility to the ATP supply in the NMJ
Author(s) -
Topaz Altman,
Danielle Geller,
Elisabeth Kleeblatt,
Tal Gradus-Perry,
Eran Perlson
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.234492
Subject(s) - biology , mitochondrion , synapse , amyotrophic lateral sclerosis , neuromuscular junction , neuroscience , microbiology and biotechnology , in vitro , biochemistry , medicine , disease
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 why the NMJ, other than its unusual dimensions, differs from other synapses. 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, 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.