title: Ultrastructural changes in muscle cells of patients with collagen VI-related myopathies.
abstract: Collagen VI is an extracellular matrix protein expressed in several tissues including skeletal muscle. Mutations in COL6A genes cause Bethlem Myopathy (BM), Ullrich Congenital Muscular Dystrophy (UCMD) and Myosclerosis Myopathy (MM). Collagen VI deficiency causes increased opening of the mitochondrial permeability transition pore (mPTP), leading to ultrastructural and functional alterations of mitochondria, amplified by impairment of autophagy. Here we report for the first time ultrastructural studies on muscle biopsies from BM and UCMD patients, showing swollen mitochondria with hypodense matrix, disorganized cristae and paracrystalline inclusions, associated with dilated sarcoplasmic reticulum and apoptotic changes. These data were supported by scanning electron microscopy analysis on BM and UCMD cultured cells, showing alterations of the mitochondrial network. Morphometric analysis also revealed a reduced short axis and depicted swelling in about 3% of mitochondria. These data demonstrate that mitochondrial defects underlie the pathogenetic mechanism in muscle tissue of patients affected by collagen VI myopathies.
authors.affiliation: SC Laboratory of Muscoloskeletal Cell Biology, IOR, Bologna, Italy; CNR- National Research Council of Italy, Institute of Molecular Genetics, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Tagliavini
authors.affiliation: SC Laboratory of Muscoloskeletal Cell Biology, IOR, Bologna, Italy; CNR- National Research Council of Italy, Institute of Molecular Genetics, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sardone
authors.affiliation: SC Laboratory of Muscoloskeletal Cell Biology, IOR, Bologna, Italy; CNR- National Research Council of Italy, Institute of Molecular Genetics, Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Squarzoni
authors.affiliation: SC Laboratory of Muscoloskeletal Cell Biology, IOR, Bologna, Italy; CNR- National Research Council of Italy, Institute of Molecular Genetics, Bologna, Italy.
authors.forename: Nadir Mario
authors.initials: NM
authors.lastname: Maraldi
authors.affiliation: SC Laboratory of Muscoloskeletal Cell Biology, IOR, Bologna, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Merlini
authors.affiliation: University of Bologna, Rizzoli Orthopaedic Institute, Bologna, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Faldini
authors.affiliation: SC Laboratory of Muscoloskeletal Cell Biology, IOR, Bologna, Italy; CNR- National Research Council of Italy, Institute of Molecular Genetics, Bologna, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Sabatelli
keywords: collagen VI; mPTP; mitochondria; scanning electron microscopy back-scattered imaging; transmission electron microscopy