Quantification of skeletal muscle mitochondrial function by ³¹P magnetic resonance spectroscopy techniques: a quantitative review

Abstract

Magnetic resonance spectroscopy (MRS) can give information about cellular metabolism in vivo which is difficult to obtain in other ways. In skeletal muscle, non-invasive (31) P MRS measurements of the post-exercise recovery kinetics of pH, [PCr], [Pi] and [ADP] contain valuable information about muscle mitochondrial function and cellular pH homeostasis in vivo, but quantitative interpretation depends on understanding the underlying physiology. Here, by giving examples of the analysis of (31) P MRS recovery data, by some simple computational simulation, and by extensively comparing data from published studies using both (31) P MRS and invasive direct measurements of muscle O2 consumption in a common analytical framework, we consider what can be learnt quantitatively about mitochondrial metabolism in skeletal muscle using MRS-based methodology. We explore some technical and conceptual limitations of current methods, and point out some aspects of the physiology which are still incompletely understood.

Evaluation of in vivo mitochondrial bioenergetics in skeletal muscle using NMR and optical methods

“…This last assumption is critical because this approach ignores changes in cellular pH, which can inhibit oxidative phosphorylation[27], during PCr recovery by focusing on the direct measurement of [PCr] from the 31 P NMR spectra. An advantage of this strategy is that it is based on the empirical relationship between the fall in PCr and resynthesis rate[27, 28] and is not dependent on a theoretical model for control of respiration. Other models for estimating ATPmax from PCr recovery data are based on either control of mitochondrial respiration by cytoplasmic [ADP][29, 30] or the free energy of ATP hydrolysis[31].…”

“…Other models for estimating ATPmax from PCr recovery data are based on either control of mitochondrial respiration by cytoplasmic [ADP][29, 30] or the free energy of ATP hydrolysis[31]. A recent review by Kemp et al[28] provides a more detailed comparison of these models for determining mitochondrial capacity from PCr recovery. In contrast to the linear model discussed above, which relies on direct measurement of [PCr] concentration from the NMR spectra, these other models require calculation of [ADP] and pH as well as knowledge of the K M for ADP, which may change under different conditions[32].…”

Impaired Mitochondrial Function and Reduced Energy Cost as a Result of Muscle Damage

“…However, one should keep in mind that the absolute initial rate of PCr resynthesis reflects the actual oxidative ATP synthesis contribution at that point, whereas the rate constant is standardly interpreted as a measure of effective mito chondrial capacity (24) for a given end-of-exercise condition (7,42). A lower rate constant might be linked to a reduced number/activity of mitochondria, an impaired vascular sup ply of 0 2 and its diffusion across the capillary wall and through the myocyte to the mitochondria (23,24). Therefore, the concomitant decrease in ATPox, l/Trecov, and Frecov PCr likely illustrates an impaired mitochondrial function as pre viously described (25).…”

Mitochondrial impairment induced by postnatal ActRIIB blockade does not alter function and energy status in exercising mouse glycolytic muscle in vivo

“…We found actually that sActRIIB-Fc treatment dramatically reduced the maximal rate of oxidative ATP synthesis (Ϫ42%), which is considered a robust and highly reproducible in vivo index of oxidative mitochondrial capacity and has been widely used in research and clinical applications (4,7,26,32). Our findings are in agreement with previous in vitro experiments conducted in wild-type mice showing that sActRIIB-Fc delivery reduces the expression of genes involved in mitochondrial oxidative phosphorylation (50,60) and decreases the level of porin, a mitochondrial membrane protein involved in the transport of ATP between mitochondrial matrix and cytosol (52).…”