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Altered mitochondrial oxidative phosphorylation capacity in horses suffering from polysaccharide storage myopathy

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Abstract

Polysaccharide storage myopathy (PSSM) is a widely described cause of exertional rhabdomyolysis in horses. Mitochondria play a central role in cellular energetics and are involved in human glycogen storage diseases but their role has been overlooked in equine PSSM. We hypothesized that the mitochondrial function is impaired in the myofibers of PSSM-affected horses. Nine horses with a history of recurrent exercise-associated rhabdomyolysis were tested for the glycogen synthase 1 gene (GYS1) mutation: 5 were tested positive (PSSM group) and 4 were tested negative (horses suffering from rhabdomyolysis of unknown origin, RUO group). Microbiopsies were collected from the gluteus medius (gm) and triceps brachii (tb) muscles of PSSM, RUO and healthy controls (HC) horses and used for histological analysis and for assessment of oxidative phosphorylation (OXPHOS) using high-resolution respirometry. The modification of mitochondrial respiration between HC, PSSM and RUO horses varied according to the muscle and to substrates feeding OXPHOS. In particular, compared to HC horses, the gm muscle of PSSM horses showed decreased OXPHOS- and electron transfer (ET)-capacities in presence of glutamate&malate&succinate. RUO horses showed a higher OXPHOS-capacity (with glutamate&malate) and ET-capacity (with glutamate&malate&succinate) in both muscles in comparison to the PSSM group. When expressed as ratios, our results highlighted a higher contribution of the NADH pathway (feeding electrons into Complex I) to maximal OXPHOS or ET-capacity in both rhabdomyolysis groups compared to the HC. Specific modifications in mitochondrial function might contribute to the pathogenesis of PSSM and of other types of exertional rhabdomyolyses.

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Authors and Affiliations

  1. Equine Sports Medicine Centre, Department of Functional Sciences, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Avenue de Cureghem, 7A (B42), Quartier Vallée 2, Sart Tilman, B-4000, Liège, Belgium

    Irene Tosi & Tatiana Art

  2. Department of pathology, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium

    Dominique Cassart

  3. Department of animal productions: Biostatistics and Bioinformatics Applied in Veterinary Sciences, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium

    Frédéric Farnir

  4. Centre of Oxygen, Research and Development, University of Liège, Liège, Belgium

    Justine Ceusters & Didier Serteyn

  5. Equine Pole, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, Liège, Belgium

    Didier Serteyn & Dominique-Marie Votion

  6. Faculty Saint-Jean, University of Alberta, Edmonton, AB, Canada

    Hélène Lemieux

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  1. Irene Tosi
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  2. Tatiana Art
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  3. Dominique Cassart
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  7. Hélène Lemieux
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  8. Dominique-Marie Votion
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Correspondence to Irene Tosi.

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Tosi, I., Art, T., Cassart, D. et al. Altered mitochondrial oxidative phosphorylation capacity in horses suffering from polysaccharide storage myopathy. J Bioenerg Biomembr 50, 379–390 (2018). https://doi.org/10.1007/s10863-018-9768-6

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  • DOI: https://doi.org/10.1007/s10863-018-9768-6

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