Changes in Muscle Cell Metabolism and Mechanotransduction Are Associated with Myopathic Phenotype in a Mouse Model of Collagen VI Deficiency

摘要: This study identifies metabolic and protein phenotypic alterations in gastrocnemius, tibialis anterior diaphragm muscles of Col6a1−/− mice, a model human collagen VI myopathies. All three mice show some common changes proteins involved metabolism, resulting decreased glycolysis the TCA cycle fluxes. These lead to different fate α-ketoglutarate, with production anabolic substrates gastrocnemius anterior, lipotoxicity diaphragm. The are associated mechanotransduction at myotendineous junction/costameric/sarcomeric level (TN-C, FAK, ROCK1, troponin I fast) energy metabolism (aldolase, enolase 3, triose phosphate isomerase, creatine kinase, adenylate kinase 1, parvalbumin, IDH1 FASN). Together, these change may explain Ca2+ deregulation, impaired force development, increased muscle-relaxation-time fiber damage found mouse as well patients. severity differs (gastrocnemius