TY - JOUR T1 - Schwann Cell Mitochondrial Metabolism Supports Long-Term Axonal Survival and Peripheral Nerve Function JF - The Journal of Neuroscience JO - J. Neurosci. SP - 10128 LP - 10140 DO - 10.1523/JNEUROSCI.0884-11.2011 VL - 31 IS - 28 AU - Andreu Viader AU - Judith P. Golden AU - Robert H. Baloh AU - Robert E. Schmidt AU - Daniel A. Hunter AU - Jeffrey Milbrandt Y1 - 2011/07/13 UR - http://www.jneurosci.org/content/31/28/10128.abstract N2 - Mitochondrial dysfunction is a common cause of peripheral neuropathies. While the role of neuron and axonal mitochondria in peripheral nerve disease is well appreciated, whether Schwann cell (SC) mitochondrial deficits contribute to peripheral neuropathies is unclear. Here, we examine how SC mitochondrial dysfunction affects axonal survival and contributes to the decline of peripheral nerve function by generating mice with SC-specific mitochondrial deficits. These mice (Tfam-SCKOs) were produced through the tissue-specific deletion of the mitochondrial transcription factor A gene (Tfam), which is essential for mitochondrial DNA (mtDNA) transcription and maintenance. Tfam-SCKOs were viable, but as they aged, they developed a progressive peripheral neuropathy characterized by nerve conduction abnormalities as well as extensive muscle denervation. Morphological examination of Tfam-SCKO nerves revealed early preferential loss of small unmyelinated fibers followed by prominent demyelination and degeneration of larger-caliber axons. Tfam-SCKOs displayed sensory and motor deficits consistent with this pathology. Remarkably, the severe mtDNA depletion and respiratory chain abnormalities in Tfam-SCKO mice did not affect SC proliferation or survival. Mitochondrial function in SCs is therefore essential for maintenance of axonal survival and normal peripheral nerve function, suggesting that SC mitochondrial dysfunction contributes to human peripheral neuropathies. ER -