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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.
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
URL: http://dx.doi.org/10.1016/j.nmd.2016.08.008
DOI: 10.1016/j.nmd.2016.08.008
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