title: Mitochondrial DNA disturbances and deregulated expression of oxidative phosphorylation and mitochondrial fusion proteins in sporadic inclusion body myositis.
abstract: Sporadic inclusion body myositis (sIBM) is one of the most common myopathies in elderly people. Mitochondrial abnormalities at the histological level are present in these patients. We hypothesize that mitochondrial dysfunction may play a role in disease aetiology. We took the following measurements of muscle and peripheral blood mononuclear cells (PBMCs) from 30 sIBM patients and 38 age- and gender-paired controls: mitochondrial DNA (mtDNA) deletions, amount of mtDNA and mtRNA, mitochondrial protein synthesis, mitochondrial respiratory chain (MRC) complex I and IV enzymatic activity, mitochondrial mass, oxidative stress and mitochondrial dynamics (mitofusin 2 and optic atrophy 1 levels). Depletion of mtDNA was present in muscle from sIBM patients and PBMCs showed deregulated expression of mitochondrial proteins in oxidative phosphorylation. MRC complex IV/citrate synthase activity was significantly decreased in both tissues and mitochondrial dynamics were affected in muscle. Depletion of mtDNA was significantly more severe in patients with mtDNA deletions, which also presented deregulation of mitochondrial fusion proteins. Imbalance in mitochondrial dynamics in muscle was associated with increased mitochondrial genetic disturbances (both depletion and deletions), demonstrating that proper mitochondrial turnover is essential for mitochondrial homoeostasis and muscle function in these patients.
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona; Internal Medicine Department, Hospital Clinic of Barcelona, CIBERER-U722, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Catalán-García
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona; Internal Medicine Department, Hospital Clinic of Barcelona, CIBERER-U722, Barcelona, Spain garrabou@clinic.ub.es.
authors.forename: Glòria
authors.initials: G
authors.lastname: Garrabou
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona; Internal Medicine Department, Hospital Clinic of Barcelona, CIBERER-U722, Barcelona, Spain.
authors.forename: Constanza
authors.initials: C
authors.lastname: Morén
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona; Internal Medicine Department, Hospital Clinic of Barcelona, CIBERER-U722, Barcelona, Spain.
authors.forename: Mariona
authors.initials: M
authors.lastname: Guitart-Mampel
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona; Internal Medicine Department, Hospital Clinic of Barcelona, CIBERER-U722, Barcelona, Spain.
authors.forename: Adriana
authors.initials: A
authors.lastname: Hernando
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, Barcelona, Spain Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Àngels
authors.initials: À
authors.lastname: Díaz-Ramos
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona; Internal Medicine Department, Hospital Clinic of Barcelona, CIBERER-U722, Barcelona, Spain.
authors.forename: Ingrid
authors.initials: I
authors.lastname: González-Casacuberta
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona; Internal Medicine Department, Hospital Clinic of Barcelona, CIBERER-U722, Barcelona, Spain.
authors.forename: Diana-Luz
authors.initials: DL
authors.lastname: Juárez
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona; Internal Medicine Department, Hospital Clinic of Barcelona, CIBERER-U722, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Bañó
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona; Internal Medicine Department, Hospital Clinic of Barcelona, CIBERER-U722, Barcelona, Spain.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Enrich-Bengoa
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, CIBERER-U727, Instituto de Investigaciones Sanitarias de Aragón, Zaragoza, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Emperador
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona; Internal Medicine Department, Hospital Clinic of Barcelona, CIBERER-U722, Barcelona, Spain.
authors.forename: José César
authors.initials: JC
authors.lastname: Milisenda
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona; Internal Medicine Department, Hospital Clinic of Barcelona, CIBERER-U722, Barcelona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Moreno
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona; Internal Medicine Department, Hospital Clinic of Barcelona, CIBERER-U722, Barcelona, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Tobías
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, Barcelona, Spain Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Zorzano
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, CIBERER-U727, Instituto de Investigaciones Sanitarias de Aragón, Zaragoza, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Montoya
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona; Internal Medicine Department, Hospital Clinic of Barcelona, CIBERER-U722, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Cardellach
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona; Internal Medicine Department, Hospital Clinic of Barcelona, CIBERER-U722, Barcelona, Spain.
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Grau
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018979:Myositis, Inclusion Body / Q000235:genetics* / Q000378:metabolism*; D010085:Oxidative Phosphorylation
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins
keywords: OPA1; deletions; depletion; mitochondria; mitofusin-2; sporadic inclusion body myositis