Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity

Ursula Fünfschilling, Lotti M. Supplie, Don Mahad, Susann Boretius, Aiman S. Saab, Julia Edgar, Bastian G. Brinkmann, Celia M. Kassmann, Iva D. Tzvetanova, Wiebke Möbius, Francisca Diaz, Dies Meijer, Ueli Suter, Bernd Hamprecht, Michael W. Sereda, Carlos T Moraes, Jens Frahm, Sandra Goebbels, Klaus Armin Nave

Research output: Contribution to journalArticle

567 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)517-521
Number of pages5
JournalNature
Volume485
Issue number7399
DOIs
StatePublished - May 24 2012

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Oligodendroglia
Myelin Sheath
Neuroglia
Axons
Lactic Acid
Central Nervous System
Farnesyltranstransferase
Muscular Atrophy
Schwann Cells
Peripheral Nervous System
Demyelinating Diseases
Glycolysis
Electron Transport Complex IV
Heme
Paralysis
Anesthetics
Respiration
Cell Death
Magnetic Resonance Spectroscopy
Inflammation

ASJC Scopus subject areas

  • General

Cite this

Fünfschilling, U., Supplie, L. M., Mahad, D., Boretius, S., Saab, A. S., Edgar, J., ... Nave, K. A. (2012). Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature, 485(7399), 517-521. https://doi.org/10.1038/nature11007

Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. / Fünfschilling, Ursula; Supplie, Lotti M.; Mahad, Don; Boretius, Susann; Saab, Aiman S.; Edgar, Julia; Brinkmann, Bastian G.; Kassmann, Celia M.; Tzvetanova, Iva D.; Möbius, Wiebke; Diaz, Francisca; Meijer, Dies; Suter, Ueli; Hamprecht, Bernd; Sereda, Michael W.; Moraes, Carlos T; Frahm, Jens; Goebbels, Sandra; Nave, Klaus Armin.

In: Nature, Vol. 485, No. 7399, 24.05.2012, p. 517-521.

Research output: Contribution to journalArticle

Fünfschilling, U, Supplie, LM, Mahad, D, Boretius, S, Saab, AS, Edgar, J, Brinkmann, BG, Kassmann, CM, Tzvetanova, ID, Möbius, W, Diaz, F, Meijer, D, Suter, U, Hamprecht, B, Sereda, MW, Moraes, CT, Frahm, J, Goebbels, S & Nave, KA 2012, 'Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity', Nature, vol. 485, no. 7399, pp. 517-521. https://doi.org/10.1038/nature11007
Fünfschilling U, Supplie LM, Mahad D, Boretius S, Saab AS, Edgar J et al. Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature. 2012 May 24;485(7399):517-521. https://doi.org/10.1038/nature11007
Fünfschilling, Ursula ; Supplie, Lotti M. ; Mahad, Don ; Boretius, Susann ; Saab, Aiman S. ; Edgar, Julia ; Brinkmann, Bastian G. ; Kassmann, Celia M. ; Tzvetanova, Iva D. ; Möbius, Wiebke ; Diaz, Francisca ; Meijer, Dies ; Suter, Ueli ; Hamprecht, Bernd ; Sereda, Michael W. ; Moraes, Carlos T ; Frahm, Jens ; Goebbels, Sandra ; Nave, Klaus Armin. / Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. In: Nature. 2012 ; Vol. 485, No. 7399. pp. 517-521.
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