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

Introduction: 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 (GYS1) 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: In 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 capacitywas 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.