Myelination and Axonal Electrical Activity Modulate the Distribution and Motility of Mitochondria at CNS Nodes of Ranvier
Open Access
- 18 May 2011
- journal article
- research article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 31 (20), 7249-7258
- https://doi.org/10.1523/jneurosci.0095-11.2011
Abstract
Energy production presents a formidable challenge to axons as their mitochondria are synthesized and degraded in neuronal cell bodies. To meet the energy demands of nerve conduction, small mitochondria are transported to and enriched at mitochondrial stationary sites located throughout the axon. In this study, we investigated whether size and motility of mitochondria in small myelinated CNS axons are differentially regulated at nodes, and whether mitochondrial distribution and motility are modulated by axonal electrical activity. The size/volume of mitochondrial stationary sites was significantly larger in juxtaparanodal/internodal axoplasm than in nodal/paranodal axoplasm. With three-dimensional electron microscopy, we observed that axonal mitochondrial stationary sites were composed of multiple mitochondria of varying length, except at nodes where mitochondria were uniformly short and frequently absent altogether. Mitochondrial transport speed was significantly reduced in nodal axoplasm compared with internodal axoplasm. Increased axonal electrical activity decreased mitochondrial transport and increased the size of mitochondrial stationary sites in nodal/paranodal axoplasm. Decreased axonal electrical activity had the opposite effect. In cerebellar axons of the myelin-deficient rat, which contain voltage-gated Na+ channel clusters but lack paranodal specializations, axonal mitochondrial motility and stationary site size were similar at Na+ channel clusters and other axonal regions. These results demonstrate juxtaparanodal/internodal enrichment of stationary mitochondria and neuronal activity-dependent dynamic modulation of mitochondrial distribution and transport in nodal axoplasm. In addition, the modulation of mitochondrial distribution and motility requires oligodendrocyte–axon interactions at paranodal specializations.Keywords
This publication has 66 references indexed in Scilit:
- Mitochondrial configurations in peripheral nerve suggest differential ATP productionJournal of Structural Biology, 2011
- Demyelination Increases Axonal Stationary Mitochondrial Size and the Speed of Axonal Mitochondrial TransportJournal of Neuroscience, 2010
- Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicatorsNature Methods, 2009
- Miro1 Is a Calcium Sensor for Glutamate Receptor-Dependent Localization of Mitochondria at SynapsesNeuron, 2009
- The Mechanism of Ca2+-Dependent Regulation of Kinesin-Mediated Mitochondrial MotilityCell, 2009
- Bidirectional Ca 2+ -dependent control of mitochondrial dynamics by the Miro GTPaseProceedings of the National Academy of Sciences of the United States of America, 2008
- Vesicular apparatus, including functional calcium channels, are present in developing rodent optic nerve axons and are required for normal node of Ranvier formationThe Journal of Physiology, 2008
- CaM kinase Iα–induced phosphorylation of Drp1 regulates mitochondrial morphologyThe Journal of cell biology, 2008
- Characterization of Oligophrenin‐1, a RhoGAP Lost in Patients Affected with Mental Retardation: Lentiviral Injection in Organotypic Brain Slice CulturesMethods in Enzymology, 2008
- Fission and selective fusion govern mitochondrial segregation and elimination by autophagyThe EMBO Journal, 2008