title: Movement and structure of mitochondria in oligodendrocytes and their myelin sheaths.
abstract: Mitochondria play several crucial roles in the life of oligodendrocytes. During development of the myelin sheath they are essential providers of carbon skeletons and energy for lipid synthesis. During normal brain function their consumption of pyruvate will be a key determinant of how much lactate is available for oligodendrocytes to export to power axonal function. Finally, during calcium-overload induced pathology, as occurs in ischemia, mitochondria may buffer calcium or induce apoptosis. Despite their important functions, very little is known of the properties of oligodendrocyte mitochondria, and mitochondria have never been observed in the myelin sheaths. We have now used targeted expression of fluorescent mitochondrial markers to characterize the location and movement of mitochondria within oligodendrocytes. We show for the first time that mitochondria are able to enter and move within the myelin sheath. Within the myelin sheath the highest number of mitochondria was in the cytoplasmic ridges along the sheath. Mitochondria moved more slowly than in neurons and, in contrast to their behavior in neurons and astrocytes, their movement was increased rather than inhibited by glutamate activating NMDA receptors. By electron microscopy we show that myelin sheath mitochondria have a low surface area of cristae, which suggests a low ATP production. These data specify fundamental properties of the oxidative phosphorylation system in oligodendrocytes, the glial cells that enhance cognition by speeding action potential propagation and provide metabolic support to axons.
authors.affiliation: Department of Anatomy, The Brain and Muscle Energy Group, University of Oslo, Oslo, Norway.|Department of Oral Biology, The Brain and Muscle Energy Group, Electron Microscopic Laboratory, University of Oslo, Oslo, Norway.|Howard Hughes Medical Institute, Ashburn, Virginia.
authors.forename: Johanne E
authors.identifier: http://orcid.org/0000-0003-3741-850X
authors.initials: JE
authors.lastname: Rinholm
authors.affiliation: Howard Hughes Medical Institute, Ashburn, Virginia.|Department of Physiology, Laboratory of Neural Computation, University of Oslo, Oslo, Norway.
authors.forename: Koen
authors.initials: K
authors.lastname: Vervaeke
authors.affiliation: Howard Hughes Medical Institute, Ashburn, Virginia.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Tadross
authors.affiliation: Howard Hughes Medical Institute, Ashburn, Virginia.
authors.forename: Ariana N
authors.initials: AN
authors.lastname: Tkachuk
authors.affiliation: Howard Hughes Medical Institute, Ashburn, Virginia.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Kopek
authors.affiliation: Howard Hughes Medical Institute, Ashburn, Virginia.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Brown
authors.affiliation: Department of Oral Biology, The Brain and Muscle Energy Group, Electron Microscopic Laboratory, University of Oslo, Oslo, Norway.
authors.forename: Linda H
authors.initials: LH
authors.lastname: Bergersen
authors.affiliation: Howard Hughes Medical Institute, Ashburn, Virginia.
authors.forename: David A
authors.initials: DA
authors.lastname: Clayton
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000378:metabolism / Q000648:ultrastructure*; D009924:Organ Culture Techniques; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D011810:Quinoxalines; D043562:Receptors, G-Protein-Coupled; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; C529424:Hcar1 protein, mouse; C512773:Olig2 protein, mouse; C056723:FG 9041
keywords: NMDA; glutamate; ischemia; metabolism; mobility; myelin; white matter