Altered Mitochondrial Oxidative Phosphorylation Capacity in Horses Suffering from Polysaccharide Storage Myopathy

Exertional myopathies are a common cause of exercise intolerance in the equine athlete, and Polysaccharide Storage Myopathy ( PSSM ) is a widely described muscular disease. It is characterized by an accumulation of abnormal glycogen in myofibers due to a genetic defect in the skeletal muscle glycogen synthase ( GYS 1) enzyme. We hypothesized that energy production through oxidative phosphorylation ( OXPHOS ) in muscular mitochondria might be impaired in type‐1 PSSM ‐affected horses. Methods Eight horses with a history of exertional rhabdomyolysis were tested for the GYS1 mutation. Muscle biopsies were collected and used for histological analysis and high resolution respirometry ( HRR ). HRR values from 3 groups of horses (5 PSSM ‐positive horses, 3 horses with a history of myopathy but PSSM ‐negative and 16 healthy controls) were compared using a linear mixed model to take into account repeated (2–3 times) measurements made for each horse. Results I n 5/8 horses histology revealed an accumulation of abnormal glycogen in myofibers. These 5 horses also tested positive for the GYS1 mutation. A severe depression of maximal OXPHOS capacity was observed by HRR in 7/8 horses with exertional rhabdomyolysis, with lower values in PSSM ‐positive cases (4/5). Conclusions Our study shows a severely decreased OXPHOS capacity in PSSM ‐affected horses. PSSM is considered primarily a defect in glycogen synthesis but altered OXPHOS might play a central role in its pathogenesis. Ethical Animal Research All study procedures were approved by the Animal Ethic Commission of the University of Liege. Sources of funding:  University of Liège. Competing interests:  none.