Nov 5, 2018

CMT disease 2A and demyelination decouple ATP and ROS production by axonal mitochondria

BioRxiv : the Preprint Server for Biology
Gerben Van HamerenNicolas Tricaud


Mitochondria are critical for the function and maintenance of myelinated axons notably through ATP production. A by-product of this activity is reactive oxygen species (ROS), which are highly deleterious for neurons. While ROS and metabolism are involved in several neurodegenerative diseases, it is still unclear how axonal activity or myelin modulates ATP and ROS production in axonal mitochondria. We imaged and quantified mitochondrial ATP and hydrogen peroxide (H2O2) in resting or stimulated peripheral nerve myelinated axons in vivo, using genetically-encoded fluorescent probes, two-photon time-lapse and CARS imaging. ATP and H2O2 productions are intrinsically higher in nodes of Ranvier even in resting conditions. Axonal firing increased both ATP and H2O2 productions but with different dynamics. In neuropathic MFN2R94Q mice, mimicking Charcot-Marie-Tooth 2A disease, defective mitochondria failed to upregulate ATP production following axonal activity. However, H2O2 production was dramatically sustained. Mimicking demyelinating peripheral neuropathy resulted in a reduced production of ATP while H2O2 level soared. Taken together, our results suggest that ATP and ROS productions are decoupled under neuropathic conditions, which ma...Continue Reading

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Mentioned in this Paper

Metabolic Process, Cellular
In Vivo
Hydrogen Peroxide
Charcot-Marie-Tooth Disease
Myelin Sheath
CHARCOT-MARIE-TOOTH Disease, Axonal, Type 2B (Disorder)
Nerve Degeneration
Fluorescent stain

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