title: Autophagy induction rescues muscular dystrophy.
abstract: Collagen VI is an extracellular matrix protein forming a microfibrillar network in the endomysium of skeletal muscles. In humans, mutations in any of the three genes coding for collagen VI cause several skeletal muscle diseases, including Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD). Collagen VI null (Col6a1(-/-)) mice display a myopathic phenotype resembling that of BM and UCMD patients. Muscles lacking collagen VI are characterized by the presence of dilated sarcoplasmic reticulum and dysfunctional mitochondria, which triggers apoptosis and leads to muscle wasting. We have found that accumulation of abnormal organelles is due to an impairment of autophagy. Reactivation of the autophagic flux by either nutritional approaches or by pharmacological and genetics tools removes dysfunctional organelles and greatly ameliorates the dystrophic phenotype.
authors.affiliation: Department of Histology, Microbiology & Medical Biotechnology, University of Padova, Padova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Grumati
authors.forename: Luisa
authors.initials: L
authors.lastname: Coletto
authors.forename: Marco
authors.initials: M
authors.lastname: Sandri
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonaldo
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D024142:Collagen Type VI / Q000235:genetics*; D016572:Cyclosporine / Q000494:pharmacology; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009132:Muscles / Q000378:metabolism; D009136:Muscular Dystrophies / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: C540085:Col6a1 protein, mouse; D024142:Collagen Type VI; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D007166:Immunosuppressive Agents; D016572:Cyclosporine