Quantifying in vivo Mitochondrial Effciency at Rest and during Exercise in Human Skeletal Muscle

Abstract

Introduction: Mitochondrial effciency provides an additional mechanism to fine-tune oxidative phosphorylation rate to match ATP demand in skeletal muscle with far-reaching consequences on exercise tolerance. However, the direct measurement of both oxygen consumption (VO2) and ATP production from the same region of the contracting muscle in vivo remains a technical challenge. Purpose: Using an innovative approach combining noninvasive phosphorus and proton magnetic resonance spectroscopy (31P/1H-MRS), the present study aimed to characterize skeletal muscle ATP synthesis rate and muscle VO2 at rest and during a graded dynamic plantar flexion exercise to determine mitochondrial effciency in the gastrocnemius muscle. Method: We assessed mitochondrial effciency in the gastrocnemius muscles of 12 healthy adults (21± 1 yrs.). 31P and 1H magnetic resonance spectroscopy (MRS) was performed using a whole-body 3T MR system (Skyra, Siemens) at rest and during a series of constant workloads coupled to brief transient ischemia to quantify both oxidative ATP synthesis (ATPox) rate and myoglobin-derived oxygen consumption (Mb-derived VO2). The MRS data were acquired with a dual-tuned 31P/1H surface coil with linear polarization positioned over the gastrocnemius muscle. Results: As expected, the end-exercise PCr concentration decreased from 29 ± 2 mM of WRmax to 18 ± 1 mM with increasing workload. Likewise, the end-exercise Mb oxygenation level declined linearly with increasing workload. As the exercise workload increased, the ATPox synthesis rate increased linearly (r2 = 0.45), whereas there was no significant change in Mb-derived VO2. At rest, the estimated P/O ratio in the gastrocnemius muscle was 1.95 ± 0.68, whereas non-physiological values were obtained during exercise. Conclusion: During exercise, Mb-derived VO2 was likely limited by O2 availability with the methodology employed (30-sec occlusion, spectrum time resolution of 10 sec), which precluded the accurate quantification of mitochondrial effciency. However, mitochondrial effciency calculated at rest is in agreement with previously documented values ex vivo and thus provides an additional parameter to evaluate mitochondrial function in vivo. This work was funded in part by National Heart, Lung, and Blood Institute Grant R00HL125756. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.