title: Changes in muscle cell metabolism and mechanotransduction are associated with myopathic phenotype in a mouse model of collagen VI deficiency.
abstract: This study identifies metabolic and protein phenotypic alterations in gastrocnemius, tibialis anterior and diaphragm muscles of Col6a1(-/-) mice, a model of human collagen VI myopathies. All three muscles of Col6a1(-/-) mice show some common changes in proteins involved in metabolism, resulting in decreased glycolysis and in changes of the TCA cycle fluxes. These changes lead to a different fate of α-ketoglutarate, with production of anabolic substrates in gastrocnemius and tibialis anterior, and with lipotoxicity in diaphragm. The metabolic changes are associated with changes of proteins involved in mechanotransduction at the myotendineous junction/costameric/sarcomeric level (TN-C, FAK, ROCK1, troponin I fast) and in energy metabolism (aldolase, enolase 3, triose phosphate isomerase, creatine kinase, adenylate kinase 1, parvalbumin, IDH1 and FASN). Together, these change may explain Ca(2+) deregulation, impaired force development, increased muscle-relaxation-time and fiber damage found in the mouse model as well as in patients. The severity of these changes differs in the three muscles (gastrocnemius<tibialis anterior<diaphragm) and correlates to the mass-to-tendon (myotendineous junction) ratio and to muscle morphology.
authors: Department of Biomedical Sciences for Health, University of Milan, Segrate (MI), Italy.
authors: Sara
authors: S
authors: De Palma
authors: Roberta
authors: R
authors: Leone
authors: Paolo
authors: P
authors: Grumati
authors: Michele
authors: M
authors: Vasso
authors: Roman
authors: R
authors: Polishchuk
authors: Daniele
authors: D
authors: Capitanio
authors: Paola
authors: P
authors: Braghetta
authors: Paolo
authors: P
authors: Bernardi
authors: Paolo
authors: P
authors: Bonaldo
authors: Cecilia
authors: C
authors: Gelfi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D024142:Collagen Type VI / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D040542:Mechanotransduction, Cellular; D051379:Mice; D032342:Muscle Cells / Q000166:cytology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013977:Tibia / Q000166:cytology / Q000378:metabolism
chemical_list: C540085:Col6a1 protein, mouse; D024142:Collagen Type VI; D002118:Calcium