Mitochondrial efficiency in resting skeletal muscle in vivo: a novel non-invasive approach using multinuclear magnetic resonance spectroscopy in humans

Abstract

Mitochondrial efficiency is a critical metabolic parameter with far-reaching implications for tissue homeostasis. However, the direct measurement of oxygen consumption (VO₂) and ATP production from a large tissue sample in vivo remains challenging. Using phosphorus (³¹P) and proton (¹H) magnetic resonance spectroscopy (MRS), this study aimed to non-invasively quantify the skeletal muscle ATP synthesis rate and VO₂ to determine mitochondrial efficiency at rest and during muscle contraction in humans. We assessed mitochondrial efficiency in the plantar flexor muscles of 12 healthy adults (21 ± 1 years) using ³¹P and ¹H MRS within a 3T MR system. MRS data were acquired at rest and during constant workloads to quantify oxidative ATP synthesis (ATP_ox) rate and myoglobin-derived oxygen consumption (Mb-derived VO₂). At rest, ATP_ox was 0.85 ± 0.24 mm min^−1, and Mb-derived VO₂ was 0.46 ± 0.11 mm min⁻¹, resulting in a P/O ratio of 1.95 ± 0.68. During graded exercise, end-exercise PCr concentration decreased from 29 ± 5.7 mm to 18 ± 4.8 mm, and end-exercise Mb oxygenation declined linearly to 47 ± 11%. ATP_ox synthesis rate increased linearly with exercise workload (r = 0.65 ± 0.31), whereas there was no significant change in Mb-derived VO₂ (r = −0.19 ± 0.60), leading to non-physiological P/O values during exercise (>3). The results indicate that combined ³¹P/¹H-MRS at rest offers a promising approach for non-invasively quantifying mitochondrial efficiency in large muscle samples, suggesting its potential as a clinical endpoint of mitochondrial function. However, further refinement is needed for use during exercise.

Key points

• Mitochondrial efficiency, converting chemical energy from carbon fuels into ATP, is a vital metabolic parameter for tissue homeostasis, but measuring oxygen consumption (VO₂) and ATP production in vivo has been challenging.
• This study used phosphorus (³¹P) and proton (¹H) magnetic resonance spectroscopy (MRS) to non-invasively quantify the skeletal muscle ATP synthesis rate and VO₂ at rest and during muscle contraction in humans.
• At rest, the oxidative ATP synthesis (ATP_ox) and myoglobin-derived VO₂ (Mb-derived VO₂) were measured, resulting in a P/O ratio of 1.95 in the plantar flexor muscles.
• During exercise, the ATP_ox rate increased with workload, but Mb-derived VO₂ did not change significantly, leading to non-physiological P/O ratios.
• The findings suggest that ³¹P/¹H-MRS at rest is a promising method for assessing mitochondrial efficiency and could be used as a clinical endpoint for mitochondrial function in vivo, although further refinement is needed for exercise conditions.