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Mitochondrial dysfunction in myofibrillar myopathy

Lookup NU author(s): Dr Amy VincentORCiD, Dr John Grady, Dr Mariana Rocha, Dr Charlotte Alston, Dr Karolina Rygiel, 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).


Myofibrillar myopathies (MFM) are characterised by focal myofibrillar destruction and accumulation of myofibrillar elements as protein aggregates. They are caused by mutations in the DES, MYOT, CRYAB, FLNC, BAG3, DNAJB6 and ZASP genes as well as other as yet unidentified genes. Previous studies have reported changes in mitochondrial morphology and cellular positioning, as well as clonally-expanded, large-scale mitochondrial DNA (mtDNA) deletions and focal respiratory chain deficiency in muscle of MFM patients. Here we examine skeletal muscle from patients with desmin (n = 6), ZASP (n = 1) and myotilin (n = 2) mutations and MFM protein aggregates, to understand how mitochondrial dysfunction may contribute to the underlying mechanisms causing disease pathology. We have used a validated quantitative immunofluorescent assay to study respiratory chain protein levels, together with oxidative enzyme histochemistry and single cell mitochondrial DNA analysis, to examine mitochondrial changes. Results demonstrate a small number of clonally-expanded mitochondrial DNA deletions, which we conclude are due to both ageing and disease pathology. Further to this we report higher levels of respiratory chain complex I and IV deficiency compared to age matched controls, although overall levels of respiratory deficient muscle fibres in patient biopsies are low. More strikingly, a significantly higher percentage of myofibrillar myopathy patient muscle fibres have a low mitochondrial mass compared to controls. We concluded this is mechanistically unrelated to desmin and myotilin protein aggregates; however, correlation between mitochondrial mass and muscle fibre area is found. We suggest this may be due to reduced mitochondrial biogenesis in combination with muscle fibre hypertrophy. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (

Publication metadata

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

Publication type: Article

Publication status: Published

Journal: Neuromuscular Disorders

Year: 2016

Volume: 26

Issue: 10

Pages: 691-701

Print publication date: 01/10/2016

Online publication date: 10/08/2016

Acceptance date: 09/08/2016

Date deposited: 17/01/2017

ISSN (print): 0960-8966

ISSN (electronic): 1873-2364

Publisher: Elsevier


DOI: 10.1016/j.nmd.2016.08.004


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Funder referenceFunder name
MR/K000608/1Medical Research Council (MRC)