Characterization of the mitochondrial function and genetics in the pathogenesis of collagen VI related disorders (958.1)

Background: Alteration in the collagen VI protein causes Bethlem Myopathy and Ullrich Congenital Muscular Dystrophy. Mitochondrial dysfunction, ultrastructural defects, increased apoptosis and autophagy impairment are associated to muscle of young Col6a1-/- mice and patients. Results: To clarify the pathophysiology of this disorder we are characterizing Col6a1-/- mice at different ages. Preliminary studies show reduced cell growth, decreased respiratory capacity, increased ROS production and increased mitochondrial mass on myoblasts isolated from old Col6a1-/- mice. Mutant cells show altered cytoskeleton structure that could explain why dysfunctional mitochondria accumulate and are not removed by autophagy. We are also determining if the progression of this myopathy is related to the accumulation of mtDNA mutations. Methods: We study: cell growth capacity, mitochondrial membrane potential and mass, oxygen consumption capacity, ROS production, mitochondrial dynamics and cytoskeleton structure in primary mu...