Effects of Hyperthermia and Acidosis on Mitochondrial Oxidative Phosphorylation.
Abstract: The intracellular environment of skeletal muscle can develop pronounced hyperthermia and acidosis during strenuous exercise, and these alterations in the typical intracellular conditions have been shown to alter mitochondrial respiration. However, the impact of these conditions on ATP synthesis is poorly understood. We used Thoroughbred racehorses to test the hypothesis that both hyperthermia and acidosis decrease the rate of ATP synthesis, but that athletic conditioning mitigates this loss of phosphorylation capacity. Isolated mitochondria were harvested from skeletal muscle before and after a 9-week racetrack conditioning program that increased whole-body aerobic capacity by 19%, and oxidative phosphorylation capacity was tested under normothermic and hyperthermic conditions, as well as normal pH and acidic pH created by the addition of lactic acid. In unfit horses, hyperthermia caused a 30-55% decrease in the rate of ATP synthesis and loss of phosphorylation efficiency (P/O ratio decreased from 4.2 to 1.7 during maximal oxidative phosphorylation). Aerobic conditioning resulted in increased phosphorylation efficiency under hyperthermic conditions. Lactic acidosis had a small negative effect on ATP synthesis in unfit horses, but aerobic conditioning increased the sensitivity of isolated mitochondria to the deleterious effects of lactic acidosis. These data support a prominent role of hyperthermia in skeletal muscle fatigue during exercise, particularly in unfit subjects. However, acidosis may be a more important cause of failure of ATP synthesis in fit subjects.
Publication Date: 2024-11-27 PubMed ID: 39601795DOI: 10.1152/japplphysiol.00418.2024Google Scholar: Lookup
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Summary
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This research article studies the impact of high temperature (hyperthermia) and high acidity (acidosis) inside muscle cells during intense exercise on ATP synthesis, the process by which our bodies produce energy. Using racehorses as their test subjects, the researchers hypothesise that both hyperthermia and acidosis disrupt ATP synthesis, but athletic conditioning can lessen this negative effect.
Objective and Methodology
- The study aims to understand the influence of hyperthermia and acidosis, conditions that typically develop in the muscular cells during strenuous exertion, on the generation of ATP (adenosine triphosphate), which is the main source of energy in cells.
- The researchers used Thoroughbred racehorses as subjects, taking isolated mitochondria – the energy-producing units in a cell – from the horse’s skeletal muscle before and after a 9-week racetrack conditioning program.
- The conditioning program was effective in increasing the horses’ whole-body aerobic capacity by 19%, thereby improving their overall fitness level.
- The harvested mitochondria were then subjected to both normal and hyperthermic (high-temperature) conditions as well as normal and acidic pH levels to test their ATP synthesis capabilities performed under these conditions.
Findings and Observations
- In horses that had not undergone the conditioning program, hyperthermia resulted in a 30-55% reduction in ATP synthesis and decreased the efficiency of phosphorylation, which is the chemical reaction involving the addition of a phosphate group that is required for ATP synthesis.
- However, the horses that went through aerobic conditioning showed an improved efficiency of phosphorylation when under hyperthermic conditions.
- Similarly, acidosis, created by the addition of lactic acid, slightly hindered ATP synthesis in unconditioned horses
- Interestingly, the aerobic conditioning made the mitochondria more vulnerable to the harmful effects of acidosis.
Conclusion
- The research concluded that hyperthermia plays a major role in muscular fatigue during exercise, especially in less fit subjects as it notably impacts ATP synthesis and phosphorylation efficiency.
- Conversely, in fitter subjects who have undergone athletic conditioning, acidosis appears to be a more dominant factor causing failure of ATP synthesis.
Cite This Article
APA
Davis MS, Bayly WM, Hansen CM, Barrett MR, Blake CA.
(2024).
Effects of Hyperthermia and Acidosis on Mitochondrial Oxidative Phosphorylation.
J Appl Physiol (1985).
https://doi.org/10.1152/japplphysiol.00418.2024 Publication
Researcher Affiliations
- Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, USA.
- Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA, USA.
- Department of Veterinary Medicine, University of Alaska Fairbanks, Fairbanks, AK, USA.
- Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, USA.
- Central Hospital for Veterinary Medicine, North Haven, CT, USA.
Grant Funding
- Grayson Jockey Club Research Foundation
- John Oxley Endowed Chair in Equine Sports Medicine
Citations
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