Mitochondria and other membranous organelles are frequently enriched in the nodes and paranodes of peripheral myelinated axons, particularly of large caliber axons. The physiological role(s) of this organelle enrichment and the rheologic factors that regulate it are not well understood. Previous studies indicate that axonal transport of organelles across the nodal/paranodal region is regulated locally. In this study, we have examined the ultrastructure of myelinated axons in the sciatic nerves of mice deficient in contactin-associated protein (Caspr), an integral junctional component. These mice, which lack the normal septate-like junctions that promote attachment of the glial (paranodal) loops to the axon, contain aberrant mitochondria in their nodal/paranodal regions. Typically, these mitochondria are large, swollen and occupy prominent varicosities of the nodal axolemma. In contrast, mitochondria outside the nodal/paranodal regions of the myelinated axons appear normal. These findings suggest that paranodal junctions regulate mitochondrial transport and function in the axoplasm of the nodal/paranodal region of myelinated axons of peripheral nerves. They further indicate that paranodal junctions might have a role, either direct or indirect, in the local regulation of energy metabolism in the nodal region.
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