Neuropathy :: Mitochondrial Trafficking and CMT2 Neuropathy

Heriditary neuropathies come in many shapes and sizes. Charcot-Marie-Tooth type 2 (CMT2) causes degeneration of peripheral sensory and motor neurons, particularly at the ends of these long axons.

Many cases of CMT2 arise from mutations in a mitochondrial fusion protein mitofusin 2 (MFN2). This week, Baloh et al. propose that MFN2 mutations cause disease by altering mitochondrial trafficking. The authors expressed mutant MFN2 in cultured dorsal root ganglion neurons. Fragmented mitochondria clustered in cell bodies and proximal axons of these neurons.

Time-lapse fluorescence imaging revealed disrupted mitochondrial trafficking, although ATP production and mitochondrial oxidative function remained intact. Likewise, oxidative activity was not disrupted in a muscle biopsy specimen from a patient with CMT2A. The transport failure may result from reduced attachment of mitochondria to the microtubule transport apparatus, thus limiting delivery of energy supplies to long axons.