Cited by 1,523Neurogenesis and neuroplasticity mechanismsMultiple Sclerosis Research StudiesMitochondrial Function and Pathology

The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.

Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity

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Abstract

Oligodendrocytes, the myelin-forming glial cells of the central nervous system, maintain long-term axonal integrity. However, the underlying support mechanisms are not understood. Here we identify a metabolic component of axon-glia interactions by generating conditional Cox10 (protoheme IX farnesyltransferase) mutant mice, in which oligodendrocytes and Schwann cells fail to assemble stable mitochondrial cytochrome c oxidase (COX, also known as mitochondrial complex IV). In the peripheral nervous system, Cox10 conditional mutants exhibit severe neuropathy with dysmyelination, abnormal Remak bundles, muscle atrophy and paralysis. Notably, perturbing mitochondrial respiration did not cause glial cell death. In the adult central nervous system, we found no signs of demyelination, axonal degeneration or secondary inflammation. Unlike cultured oligodendrocytes, which are sensitive to COX inhibitors, post-myelination oligodendrocytes survive well in the absence of COX activity. More importantly, by in vivo magnetic resonance spectroscopy, brain lactate concentrations in mutants were increased compared with controls, but were detectable only in mice exposed to volatile anaesthetics. This indicates that aerobic glycolysis products derived from oligodendrocytes are rapidly metabolized within white matter tracts. Because myelinated axons can use lactate when energy-deprived, our findings suggest a model in which axon-glia metabolic coupling serves a physiological function.

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Metadata

Authors
Fünfschilling, U., Supplie, L. M., Mahad, D., Boretius, S., Saab, A. S., Edgar, J., Brinkmann, B. G., Kassmann, C. M., Tzvetanova, I. D., Möbius, W., Diaz, F., Meijer, D., Suter, U., Hamprecht, B., Sereda, M. W., Moraes, C. T., Frahm, J., Goebbels, S., & Nave, K.-A.
Affiliations
  • Max Planck Institute of Experimental Medicine (DE)
  • Max Planck Society (DE)
  • Newcastle University (GB)
  • Erasmus MC (NL)
  • ETH Zurich (CH)
  • University of Miami (US)
Corresponding author
Nave, Klaus-Armin
Venue
Nature
Published
2012-04-29
Volume
485
Issue
7399
Pages
517-521
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2085029391
Cited by
1,523
References
33
Citations by year
2026: 121 · 2025: 120 · 2024: 127 · 2023: 107 · 2022: 125 · 2021: 142 · 2020: 121 · 2019: 107 · 2018: 91 · 2017: 128 · 2016: 95 · 2015: 93 · 2014: 64 · 2013: 65 · 2012: 13
FWCI
25.34
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
  • GRO (submittedVersion, cc-by)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
Wellcome Trust (078415)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
oligodendrocytes, myelination, aerobic glycolysis, lactate, mitochondrial cytochrome c oxidase, COX10, axonal integrity, demyelination, Schwann cells, white matter, brain lactate, mitochondrial respiration
MeSH terms
Action Potentials, Animals, Axons, Brain, Cell Survival, Electron Transport Complex IV, Demyelinating Diseases, Glycolysis, Membrane Proteins, Mitochondria, Myelin Sheath, Magnetic Resonance Spectroscopy, Oligodendroglia, Protons, Schwann Cells, Time Factors, Cell Respiration, Lactic Acid, Alkyl and Aryl Transferases, Mutant Proteins, Mice

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