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

This research looks into the potential role of mitochondria in horses suffering from Polysaccharide storage myopathy (PSSM), a common cause of exercise-associated muscle breakdown (rhabdomyolysis), and reports that the mitochondrial function seems to be impaired in such horses.

Introduction and Hypothesis

• The paper begins by describing the significance of PSSM in horses that causes rhabdomyolysis, which is the breakdown of muscle tissues during exertion. This condition has been widely documented in veterinary medicine.
• Despite the central role of mitochondria in generating cellular energy and their known involvement in human glycogen storage diseases, they have not been extensively studied in the context of PSSM in horses.
• The researchers hypothesize that mitochondrial function might be disrupted in the muscle fibers (myofibers) of horses affected by PSSM.

Study Design and Methodology

• Nine horses, with a history of repeated exertion-related rhabdomyolysis, were tested for the GYS1 gene mutation associated with PSSM.
• Five horses tested positive (forming the PSSM group) whereas the other four who tested negative, formed the group of horses experiencing rhabdomyolysis of an undetermined cause (RUO group).
• Microbiopsies were taken from specific muscles of these horses – the gluteus medius (gm) and triceps brachii (tb). These samples were used for histological analysis and tested for oxidative phosphorylation (OXPHOS), a mitochondrial process generating cellular energy, using high-resolution respirometry.

Findings

• Differences in mitochondrial respiration were observed between the healthy control horses (HC), PSSM, and RUO group horses. These differences varied depending on the muscle examined and the substrates used to fuel OXPHOS.
• Specifically, the gm muscle from PSSM horses showed a decreased OXPHOS and electron transfer (ET) capacities when compared to healthy control horses in the presence of certain mitochondrial substrates (glutamate, malate, and succinate).
• On the contrary, the RUO horses displayed higher OXPHOS and ET capacities in both muscle types when compared to the PSSM group in presence of these substrates.
• When analysed as ratios, the results indicated that both the PSSM and RUO groups had a greater contribution from the NADH pathway, that introduces electrons into Complex I of the mitochondrial electron transport chain, to maximum OXPHOS or ET capacity when compared to healthy horses.
• Such specific changes in mitochondrial functionality might contribute to the onset of PSSM and other types of exertional rhabdomyolysis.

Conclusion

• This research suggests mitochondrial dysfunction in horses affected by PSSM, as seen by the decreased OXPHOS and ET capacities in certain muscle tissues.
• These findings merit further research to explore the mechanism of PSSM and other types of exertional rhabdomyolysis in horses.