Mutation in dystrophin-encoding gene affects energy metabolism in mouse myoblasts

Duchenne Muscular Dystrophy is characterized by severe defects in differentiated Muscle fibers, including abnormal Calcium homeostasis and impaired cellular energy metabolism. Here we demonstrate that myoblasts derived from dystrophic (mdx) mouse exhibit reduced oxygen consumption, increased mitochondrial membrane potential, enhanced reactive oxygen species formation, stimulated glycolysis but unaffected total cellular ATP content. Moreover, reduced amounts Of Specific Subunits of the mitochondrial respiratory complexes and ATP-synthase as well as disorganized mitochondrial network were observed, Both the dystrophic and control myoblasts used were derived from a common inbred mouse strain and the only difference between them is a point Mutation in the dystrophin-encoding gene, thus these data indicate that this mutation results ill Multiple phenotypic alterations demonstrating as early as in undifferentiated myoblasts. This finding sheds new light on the molecular mechanisms of Duchenne Muscular Dystrophy pathogenesis. (C) 2009 Elsevier Inc. All rights reserved.