Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

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

Gerben van Hameren, Graham Campbell, Marie Deck, Jade Berthelot, Roman Chrast, Nicolas Tricaud
doi: https://doi.org/10.1101/462523
Gerben van Hameren
1Institut des Neurosciences de Montpellier, INSERM U1051, Université de Montpellier, Montpellier, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: gerben.van-hameren@inserm.fr nicolas.tricaud@inserm.fr
Graham Campbell
1Institut des Neurosciences de Montpellier, INSERM U1051, Université de Montpellier, Montpellier, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marie Deck
1Institut des Neurosciences de Montpellier, INSERM U1051, Université de Montpellier, Montpellier, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jade Berthelot
1Institut des Neurosciences de Montpellier, INSERM U1051, Université de Montpellier, Montpellier, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roman Chrast
2Departments of Neuroscience and Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nicolas Tricaud
1Institut des Neurosciences de Montpellier, INSERM U1051, Université de Montpellier, Montpellier, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: gerben.van-hameren@inserm.fr nicolas.tricaud@inserm.fr
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

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 may compromise axonal function and integrity.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Back to top
PreviousNext
Posted December 04, 2018.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
CMT disease 2A and demyelination decouple ATP and ROS production by axonal mitochondria
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
CMT disease 2A and demyelination decouple ATP and ROS production by axonal mitochondria
Gerben van Hameren, Graham Campbell, Marie Deck, Jade Berthelot, Roman Chrast, Nicolas Tricaud
bioRxiv 462523; doi: https://doi.org/10.1101/462523
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
CMT disease 2A and demyelination decouple ATP and ROS production by axonal mitochondria
Gerben van Hameren, Graham Campbell, Marie Deck, Jade Berthelot, Roman Chrast, Nicolas Tricaud
bioRxiv 462523; doi: https://doi.org/10.1101/462523

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (4684)
  • Biochemistry (10361)
  • Bioengineering (7677)
  • Bioinformatics (26337)
  • Biophysics (13530)
  • Cancer Biology (10687)
  • Cell Biology (15444)
  • Clinical Trials (138)
  • Developmental Biology (8498)
  • Ecology (12822)
  • Epidemiology (2067)
  • Evolutionary Biology (16865)
  • Genetics (11400)
  • Genomics (15480)
  • Immunology (10617)
  • Microbiology (25221)
  • Molecular Biology (10224)
  • Neuroscience (54478)
  • Paleontology (402)
  • Pathology (1668)
  • Pharmacology and Toxicology (2897)
  • Physiology (4344)
  • Plant Biology (9249)
  • Scientific Communication and Education (1586)
  • Synthetic Biology (2558)
  • Systems Biology (6781)
  • Zoology (1466)