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.

β-aminoisobutyric Acid, l-BAIBA, Is a Muscle-Derived Osteocyte Survival Factor

“…As mitochondria are known to produce ROS as a by-product along with the production of ATP, we decided to determine if mitochondria might be involved in the protective effects of BAIBA on H 2 O 2 -induced cell death. Using Mito Red, we found that mitochondria can be imaged over time in MLO-Y4 cells and mitochondria can be observed moving in the dendritic processes, similar to that observed with oligodendrocyte primary processes and neuronal dendrites (Rinholm et al, 2016) (Figure 7A; Movies S1 and S2). Primary osteocytes isolated from Dmp1-GFP mice showed similar properties with regard to mitochondrial movement (Figure 7A; Movie S3).…”

“…Mitochondria show massive fragmentation of their network associated with cytochrome c release, which induces the formation of the apoptosome leading to activation of caspase-3, responsible for apoptosis (Langlais et al, 2015). We were able to image mitochondria in both MLO-Y4 cells and primary osteocytes, showing trafficking similar to that observed in axonal neural cells (Rinholm et al, 2016). Here we show that BAIBA prevented or reduced this massive breakdown of mitochondria induced by H 2 O 2 in MLO-Y4 osteocyte-like cells.…”

Inhibition of Drp1 hyper-activation is protective in animal models of experimental multiple sclerosis

“…Mitochondria have been found to be located in different compartments of the OLs including soma, primary processes and the cytoplasmic channels of the myelin sheath (Rinholm et al, 2016). The proper functioning of mitochondria in OLs is critical for their cellular integrity.…”

Glutamate signalling: A multifaceted modulator of oligodendrocyte lineage cells in health and disease

“…Mature oligodendrocytes respond to neuronal stimulation by a calcium rise in myelin only when both AMPA and NMDA receptors work in concert (Micu et al, 2016). Moreover, NMDA receptor activation regulates mitochondria movement within the myelin sheath (Rinholm et al, 2016), presumably to provide energy to myelin sheaths wrapped around the most active axons and to coordinate myelin synthesis (Rinholm et al, 2011). This suggests that glutamate signalling may not only be important for the initiation and completion of differentiation, but also for myelin maintenance and plasticity.…”