Movement and structure of mitochondria in oligodendrocytes and their myelin sheaths

TY - JOUR

T1 - Movement and structure of mitochondria in oligodendrocytes and their myelin sheaths

AU - Rinholm, Johanne E

AU - Vervaeke, Koen

AU - Tadross, Michael R

AU - Tkachuk, Ariana N

AU - Kopek, Benjamin G

AU - Brown, Timothy A

AU - Bergersen, Linda H

AU - Clayton, David A

N1 - © 2016 Wiley Periodicals, Inc.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

KW - Animals

KW - Animals, Newborn

KW - Basic Helix-Loop-Helix Transcription Factors/metabolism

KW - Cytoplasm/metabolism

KW - Excitatory Amino Acid Antagonists/pharmacology

KW - Glutamic Acid/pharmacology

KW - In Vitro Techniques

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Mitochondria/drug effects

KW - Myelin Basic Protein/genetics

KW - Myelin Sheath/physiology

KW - Nerve Tissue Proteins/metabolism

KW - Oligodendrocyte Transcription Factor 2

KW - Oligodendroglia/metabolism

KW - Organ Culture Techniques

KW - Quinoxalines/pharmacology

KW - Rats

KW - Rats, Wistar

KW - Receptors, G-Protein-Coupled/genetics

KW - Sodium Channel Blockers/pharmacology

KW - Tetrodotoxin/pharmacology

U2 - 10.1002/glia.22965

DO - 10.1002/glia.22965

M3 - Journal article

C2 - 26775288

SN - 0894-1491

VL - 64

SP - 810

EP - 825

JO - Glia

JF - Glia

IS - 5

ER -