TY - JOUR

T1 - Combined changes in temperature and pH mimicking exercise result in decreased efficiency in muscle mitochondria

AU - Flensted-Jensen, Mathias

AU - Kleis-Olsen, Ann Sofie

AU - Hassø, Rasmus Kinimond

AU - Lindtofte, Søren

AU - Corral Pérez, Juan

AU - Ortega-Gómez, Sonia

AU - Larsen, Steen

PY - 2024

Y1 - 2024

N2 - It is well known that exercise efficiency declines at intensities above the lactate threshold, yet the underlying mechanisms are poorly understood. Some have suggested it is due to a decline in mitochondrial efficiency, but this is difficult to examine in vivo. Therefore, the aim of the current study was to examine how changes in temperature and pH, mimicking those that occur during exercise, affect mitochondrial efficiency in skeletal muscle mitochondria. This study was performed on quadriceps muscle of 20 wild-type mice. Muscle tissue was dissected and either permeabilized (n = 10) or homogenized for isolation of mitochondria (n = 10), and oxidative phosphorylation capacity and P/O ratio were assessed using high-resolution respirometry. Samples from each muscle were analyzed in both normal physiological conditions (37°C, pH 7.4), decreased pH (6.8), increased temperature (40°C), and a combination of both. The combination of increased temperature and decreased pH resulted in a significantly lower P/O ratio, mirrored by an increase in leak respiration and a decrease in respiratory control ratio (RCR), in isolated mitochondria. In permeabilized fibers, RCR and leak were relatively unaffected, though a main effect of temperature was observed. Oxidative phosphorylation capacity was unaffected by changes in pH and temperature in both isolated mitochondria and permeabilized fibers. These results indicate that exercise-like changes in temperature and pH lead to impaired mitochondrial efficiency. These findings offer some degree of support to the concept of decreased mitochondrial efficiency during exercise, and may have implications for the assessment of mitochondrial function related to exercise.NEW & NOTEWORTHY To the best of our knowledge, this is the first study to examine the effects of combined changes in temperature and pH, mimicking intramuscular alterations during exercise. Our findings suggest that mitochondrial efficiency is impaired during exercise of moderate to high intensity, which could be a possible mechanism contributing to the decline in exercise efficiency at intensities above the lactate threshold.

AB - It is well known that exercise efficiency declines at intensities above the lactate threshold, yet the underlying mechanisms are poorly understood. Some have suggested it is due to a decline in mitochondrial efficiency, but this is difficult to examine in vivo. Therefore, the aim of the current study was to examine how changes in temperature and pH, mimicking those that occur during exercise, affect mitochondrial efficiency in skeletal muscle mitochondria. This study was performed on quadriceps muscle of 20 wild-type mice. Muscle tissue was dissected and either permeabilized (n = 10) or homogenized for isolation of mitochondria (n = 10), and oxidative phosphorylation capacity and P/O ratio were assessed using high-resolution respirometry. Samples from each muscle were analyzed in both normal physiological conditions (37°C, pH 7.4), decreased pH (6.8), increased temperature (40°C), and a combination of both. The combination of increased temperature and decreased pH resulted in a significantly lower P/O ratio, mirrored by an increase in leak respiration and a decrease in respiratory control ratio (RCR), in isolated mitochondria. In permeabilized fibers, RCR and leak were relatively unaffected, though a main effect of temperature was observed. Oxidative phosphorylation capacity was unaffected by changes in pH and temperature in both isolated mitochondria and permeabilized fibers. These results indicate that exercise-like changes in temperature and pH lead to impaired mitochondrial efficiency. These findings offer some degree of support to the concept of decreased mitochondrial efficiency during exercise, and may have implications for the assessment of mitochondrial function related to exercise.NEW & NOTEWORTHY To the best of our knowledge, this is the first study to examine the effects of combined changes in temperature and pH, mimicking intramuscular alterations during exercise. Our findings suggest that mitochondrial efficiency is impaired during exercise of moderate to high intensity, which could be a possible mechanism contributing to the decline in exercise efficiency at intensities above the lactate threshold.

KW - exercise

KW - mitochondria

KW - mitochondrial efficiency

KW - pH

KW - temperature

U2 - 10.1152/japplphysiol.00293.2023

DO - 10.1152/japplphysiol.00293.2023

M3 - Journal article

C2 - 37969081

AN - SCOPUS:85181176798

VL - 136

SP - 79

EP - 88

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

SN - 8750-7587

IS - 1

ER -