Proper regulation of mitochondrial fusion and fission is required for both neurons and Schwann cells, report Niemann et al. on page 1067.
Charcot-Marie-Tooth disease (CMT) is subdivided into axonal or demyelinating phenotypes, depending on whether the neurons or the myelinating Schwann cells are most affected. However, mutations in a single gene, GDAP1, can cause both phenotypes, muddying the distinction.
Niemann et al. found that GDAP1 is localized to the outer membrane of mitochondria. Overexpression of wild-type GDAP1 caused excessive fragmentation of mitochondria, whereas knock-down of GDAP1 expression resulted in long tubular mitochondria. Disease-causing mutations also impaired mitochondrial fission. However, mitochondrial physiology was not obviously disrupted in the presence of excess GDAP1 or GDAP1 mutations, leaving open the question of why the mutations induce degeneration.
GDAP1 is not the first protein involved in mitochondrial dynamics to be associated with CMT. Mutations in Mfn2, a protein...
