Journal article

Metabolic remodeling of dystrophic skeletal muscle reveals biological roles for dystrophin and utrophin in adaptation and plasticity

Justin P Hardee, Karen JB Martins, Paula M Miotto, James G Ryall, Stefan M Gehrig, Boris Reljic, Timur Naim, Jin D Chung, Jen Trieu, Kristy Swiderski, Ashleigh M Philp, Andrew Philp, Matthew J Watt, David A Stroud, Rene Koopman, Gregory R Steinberg, Gordon S Lynch

Molecular Metabolism | ELSEVIER | Published : 2021

Abstract

OBJECTIVES: Preferential damage to fast, glycolytic myofibers is common in many muscle-wasting diseases, including Duchenne muscular dystrophy (DMD). Promoting an oxidative phenotype could protect muscles from damage and ameliorate the dystrophic pathology with therapeutic relevance, but developing efficacious strategies requires understanding currently unknown biological roles for dystrophin and utrophin in dystrophic muscle adaptation and plasticity. METHODS: Combining whole transcriptome RNA sequencing and mitochondrial proteomics with assessments of metabolic and contractile function, we investigated the roles of dystrophin and utrophin in fast-to-slow muscle remodeling with low-frequenc..

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Grants

Awarded by National Health and Medical Research Council


Funding Acknowledgements

We gratefully acknowledge the assistance and advice from Dr. Charles T. Putman, Dr. Kelvin E. Jones, and Zoltan Kenwell (electronics specialist) from the University of Alberta when establishing the wireless stimulator model with K.J.M. during the development phase of the project. J.P.H was supported by a McKenzie Research Fellowship from The University of Melbourne. P.M.M was supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) Post-Doctoral Fellowship. This work was supported by research grants from the National Health and Medical Research Council (GNT1124474; GNT1140906; GNT1140851), The University of Melbourne's School of Biomedical Sciences Early-Mid Career Research Association (EMCRA) Collaborative Award, and The University of Melbourne's Medicine, Dentistry, and Health Sciences Large Equipment Grant Scheme. We thank the Bio21 Mass Spectrometry and Proteomics Facility (MMSPF) for the provision of instrumentation, training, and technical support.