Treatment of mitochondrial dysfunction in patients with collagen VI mutations.

In two previous editorials (Olsen, 2003, 2007) I highlighted studies of the intriguing pathogenetic mechanisms by which mutations in collagen VI cause Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD) in humans. In studies of Col6a1 deficient mice, Irwin et al. (2003) discovered that an unexpected collagen/mitochondrial connection may explain their Bethlem-like myopathy. When Col6a1 null muscle fibers were incubated with the mitochondrial ATP synthase inhibitor oligomycin, the investigators (Irwin et al., 2003) found evidence of mitochondrial depolarization, Ca~(++)-deregulation and increased apoptosis. The effects could be reversed by either incubating Col6a1 null muscle fibers with cyclosporin A, an inhibitor of the mitochondrial permeability pore, or by plating the cells on collagen VI. Finally, Irwin et al. (2003) found that treatment of the Col6a1 null mice with cyclosporin A rescued the muscle phenotype in vivo. In 2007, Angelin et al. (2007) took these exciting studies a step further by demonstrating that muscle biopsies from five patients with UCMD, in which muscle tissue contained no or severely reduced levels of collagen VI, also showed an abnormal mitochondrial depolarization response to oligomycin and that plating the cells on collagen VI or treatment with cyclosporin A normalized the mitochondrial phenotype.

作 者：

Olsen,BR

刊 名：

Matrix biology 

年，卷(期)：

2008vol.27(no.4) 

分类号：

 

关键词：

VI  Functional disorder  Therapeutic procedure  Collagen  胶原

正文语种：

eng 

基金项目：