Toggle Main Menu Toggle Search

Open Access padlockePrints

Dysferlin mutations and mitochondrial dysfunction

Lookup NU author(s): Dr Amy VincentORCiD, Hannah Rosa, Dr Charlotte Alston, Dr John Grady, Dr Karolina Rygiel, Dr Mariana Rocha, Dr Rita Barresi, Professor Robert Taylor, Emeritus Professor Doug Turnbull



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Dysferlinopathies are caused by mutations in the DYSF gene and patients may present with proximal or distal myopathy. Dysferlin is responsible for membrane resealing, and mutations may result in a defect in membrane repair following mechanical or chemical stress, causing an influx of Ca2+. Since mitochondria are involved in Ca2+ buffering, we hypothesised that mitochondrial defects may be present in skeletal muscle biopsies from patients with mutations in this gene. The aim was to characterise mitochondrial defects in muscle from patients with dysferlinopathies. Here, we analysed skeletal muscle biopsies for eight patients by quadruple immunofluorescent assay to assess oxidative phosphorylation protein abundance. Long-range PCR in single muscle fibres was used to look for presence of clonally expanded large-scale mitochondrial DNA rearrangements in patients' skeletal muscle (n = 3). Immunofluorescence demonstrated that the percentage of complex I- and complex IV-deficient fibres was higher in patients with DYSF mutations than in age-matched controls. No clonally expanded mtDNA deletions were detected using long-range PCR in any of the analysed muscle fibres. We conclude that complex I and complex IV deficiency is higher in patients than age matched controls but patients do not have rearrangements of the mtDNA. We hypothesise that respiratory chain deficiency may be the results of an increased cytosolic Ca2+ concentration (due to a membrane resealing defect) causing mitochondrial aberrations. (C) 2016 The Authors. Published by Elsevier B.V.

Publication metadata

Author(s): Vincent AE, Rosa HS, Alston CL, Grady JP, Rygiel KA, Rocha MC, Barresi R, Taylor RW, Turnbull DM

Publication type: Article

Publication status: Published

Journal: Neuromuscular Disorders

Year: 2016

Volume: 26

Issue: 11

Pages: 782-788

Print publication date: 01/11/2016

Online publication date: 29/08/2016

Acceptance date: 15/08/2016

Date deposited: 18/01/2017

ISSN (print): 0960-8966

ISSN (electronic): 1873-2364

Publisher: Elsevier


DOI: 10.1016/j.nmd.2016.08.008


Altmetrics provided by Altmetric


Funder referenceFunder name
Lily Foundation
UK NHS Highly Specialised Commissioners
UK NIHR Biomedical Research Centre in Age and Age Related Diseases award
096919Z/11/ZWellcome Trust Centre for Mitochondrial Research
G0601943Medical Research Council (UK) Centre for Translational Muscle Disease Research
MR/K000608/1MRC studentship as part of the MRC Centre for Neuromuscular Disease
NIHR-HCS-D12-03-04National Institute for Health Research (NIHR) doctoral fellowship
MR/K501074/1MRC studentship as part of the MRC Centre for Neuromuscular Disease