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

Abstract

It is now clear that mitochondria are involved as either a cause or consequence of many chronic diseases. This central role of mitochondria is due to their position in the cell as important integrators of cellular energetics and signaling. Mitochondrial function affects many aspects of the cellular environment such as redox homeostasis and calcium signaling, which then also exert control over mitochondrial function. This complex dynamic between mitochondrial function and the cellular environment highlights the value of examining mitochondria in vivo in the intact physiological environment. This review discusses NMR and optical approaches used to measure mitochondria ATP and oxygen fluxes that provide in vivo measures of mitochondrial capacity and quality in animal and human models. Combining these in vivo measurements with more traditional ex vivo analyses can lead to new insights into the importance of the cellular environment in controlling mitochondrial dysfunction under pathological conditions. Interpretation and underlying assumptions for each technique are discussed with the goal of providing an overview of some of the most common approaches used to measure in vivo mitochondrial function encountered in the literature.

Human iPSC-Derived Neural Progenitors Are an Effective Drug Discovery Model for Neurological mtDNA Disorders

“…This suggests that cells carrying the m.9185T>C mutation had efficiently adapted their energy expenditure to the lower levels of ATP. This behavior also is encountered in physiological conditions of energy shortage (Staples and Buck, 2009), and it is also in agreement with clinical observations (Campbell and Marcinek, 2016). One of these cellular adjustments probably involves the partial depolarization of the plasma membrane , as we observed in NPC_ATP6 using electrophysiology analysis ( Figure 4F).…”

Feeding mitochondria: Potential role of nutritional components to improve critical illness convalescence

“…Therefore, this field of research would greatly benefit from in vivo (non-invasive) real-time assessments of mitochondrial function. Approaches that could be used are 1) indirect calorimetry to measure in vivo substrate oxidation [156], 2) Phosphorus NMR spectroscopy to measure phosphocreatine, ATP, inorganic phosphate, and 3) near-infrared spectroscopy (NIRS) to measure in vivo muscle oxygen consumption [157]. This altogether provides a wealth of information on in vivo mitochondrial functioning.…”

Assessing tissue metabolism by phosphorous-31 magnetic resonance spectroscopy and imaging: a methodology review

“…Applications of these techniques to the investigation of a specific physiology/pathology will be discussed without detailed description. Interested readers are referred to recent review articles on the applications of 31 P-MRS/MRI in metabolic characterization of skeletal muscle (10)(11)(12), heart (13), brain (14), and liver (11), as well as in diseases such as cancer (15), heart failure (16), and obesity and diabetes (17,18).…”