title: Mutation in dystrophin-encoding gene affects energy metabolism in mouse myoblasts.
abstract: 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 in multiple phenotypic alterations demonstrating as early as in undifferentiated myoblasts. This finding sheds new light on the molecular mechanisms of Duchenne Muscular Dystrophy pathogenesis.
authors.affiliation: Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Onopiuk
authors.forename: Wojciech
authors.initials: W
authors.lastname: Brutkowski
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wierzbicka
authors.forename: Sylwia
authors.initials: S
authors.lastname: Wojciechowska
authors.forename: Joanna
authors.initials: J
authors.lastname: Szczepanowska
authors.forename: Jan
authors.initials: J
authors.lastname: Fronk
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.forename: Dariusz C
authors.initials: DC
authors.lastname: Górecki
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Zabłocki
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics*; D006019:Glycolysis / Q000235:genetics; D051379:Mice; D018101:Mice, Inbred mdx; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism*; D010101:Oxygen Consumption / Q000235:genetics; D017354:Point Mutation
chemical_list: D016189:Dystrophin; D000255:Adenosine Triphosphate; D025261:Mitochondrial Proton-Translocating ATPases