On the pathogenesis of collagen VI muscular dystrophies - Comment on article of Hicks et al

This letter to the Editor addresses the bases for the apparent discrepancy between our published work and a report by Hicks et al (Brain 2009, 132: 147–155). While confirming our finding that myoblasts from patients affected by Ullrich congenital muscular dystrophy (UCMD) display a latent mitochondrial dysfunction that can be unmasked by the addition of the F1FO ATPase inhibitor oligomycin (Angelin et al., 2007 Proc Natl Acad Sci USA 104: 991–6), Hicks et al. conclude that ‘PTP dysregulation may be a particular characteristic of the state of these cells in culture and is not specific to the collagen VI defect’. We extensively argue on the basis for this discrepancy, which is mostly non substantial, and conclude that the results of Hicks et al. (2009) reinforce our original suggestion that mitochondria play a key pathogenic role in UCMD and possibly other forms of muscular dystrophy, and that the permeability transition pore is a viable target for therapeutic intervention as shown in our earlier publications (Irwin et al. Nat Genet 2003 35: 267–7; Angelin et al., 2007 Proc Natl Acad Sci USA 104: 991–6; Merlini et al., 2008 Proc Natl Acad Sci USA 105: 5225–29; Angelin et al., 2008 Biochim Biophys Acta Bioenergetics 1777: 893–6).