Significance Degeneration of demyelinated axons is a major cause of permanent neurological disability in primary diseases of myelin. In addition to myelin loss, dysfunction of axonal mitochondria may be an essential requisite for degeneration of demyelinated axons. Here we describe a significant increase in axonal mitochondrial volume following demyelination of CNS axons. A deficiency in tethering mitochondria to the cytoskeleton prevented this volume increase in demyelinated axons and increased axonal degeneration, which was rescued by pharmacological inhibition of nerve transmission along the demyelinated axon. These results demonstrate that ( i ) increasing mitochondrial volume in CNS demyelinated axons protects against axonal degeneration and ( ii ) immobilization of mitochondria is required for the increase in axonal mitochondria volume following CNS demyelination.
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Ohno et al. (2014) studied this question.