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. 2016 Dec:10:65-77.
doi: 10.1016/j.redox.2016.09.009. Epub 2016 Sep 21.

Blood cell respirometry is associated with skeletal and cardiac muscle bioenergetics: Implications for a minimally invasive biomarker of mitochondrial health

Daniel J Tyrrell  1 , Manish S Bharadwaj  1 , Matthew J Jorgensen  2 , Thomas C Register  2 , Anthony J A Molina  3
Affiliations

Blood cell respirometry is associated with skeletal and cardiac muscle bioenergetics: Implications for a minimally invasive biomarker of mitochondrial health

Daniel J Tyrrell et al. Redox Biol. 2016 Dec.

Abstract

Blood based bioenergetic profiling strategies are emerging as potential reporters of systemic mitochondrial function; however, the extent to which these measures reflect the bioenergetic capacity of other tissues is not known. The premise of this work is that highly metabolically active tissues, such as skeletal and cardiac muscle, are susceptible to differences in systemic bioenergetic capacity. Therefore, we tested whether the respiratory capacity of blood cells, monocytes and platelets, are related to contemporaneous respirometric assessments of skeletal and cardiac muscle mitochondria. 18 female vervet/African green monkeys (Chlorocebus aethiops sabaeus) of varying age and metabolic status were examined for this study. Monocyte and platelet maximal capacity correlated with maximal oxidative phosphorylation capacity of permeabilized skeletal muscle (R=0.75, 95% confidence interval [CI]: 0.38-0.97; R=0.51, 95%CI: 0.05-0.81; respectively), isolated skeletal muscle mitochondrial respiratory control ratio (RCR; R=0.70, 95%CI: 0.35-0.89; R=0.64, 95%CI: 0.23-0.98; respectively), and isolated cardiac muscle mitochondrial RCR (R=0.55, 95%CI: 0.22-0.86; R=0.58, 95%CI: 0.22-0.85; respectively). These results suggest that blood based bioenergetic profiling may be used to report on the bioenergetic capacity of muscle tissues. Blood cell respirometry represents an attractive alternative to tissue based assessments of mitochondrial function in human studies based on ease of access and the minimal participant burden required by these measures.

Keywords: Bioenergetics; Blood cells; Cellular respiration; Mitochondria; Muscle.

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Figures

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Graphical abstract
Fig. 1.
Fig. 1
Representative bioenergetic profiles from CD14+ monocytes, platelets, skeletal muscle isolated mitochondria, cardiac isolated mitochondria, and permeabilized skeletal muscle fibers from one animal. Respiration is measured as oxygen consumption rate (pmol/min/250,000 cells [monocytes], pmol/min/mg protein [platelets], pmol/min/5 µg mitochondrial protein [left vastus and cardiac tissues]), and pmol/min/mg dry weight [permeabilized fibers]. In isolated mitochondrial preparations, complex II (CII) respiration was measured using succinate and rotenone as substrates. Ama=antimycin-A, c=cytochrome c, D=adenosine diphosphate, F=carbonyl-cyanide-p-trifluoromethoxyphenylhydrazone, G=glutamate, M=malate, O=oligomycin, P=pyruvate, R=rotenone, S=succinate, U=uncoupler (FCCP).
Fig. 2.
Fig. 2
Associations among CD14+ monocyte bioenergetic parameters with skeletal and cardiac muscle bioenergetics. Regressions between monocyte maximal uncoupled respiration and reserve capacity with respiratory control ratio and maximal uncoupled respiration from isolated mitochondria from skeletal and cardiac muscle as well as maximal oxidative phosphorylation capacity and maximal uncoupled respiration from permeabilized skeletal muscle fibers. Pearson's correlations and p-values for each association are shown.
Fig. 3.
Fig. 3
Associations among platelet bioenergetic parameters with skeletal and cardiac muscle bioenergetics. Regressions between platelet maximal uncoupled respiration and reserve capacity with respiratory control ratio and maximal uncoupled respiration from isolated mitochondria from skeletal and cardiac muscle as well as maximal oxidative phosphorylation capacity and maximal uncoupled respiration from permeabilized skeletal muscle fibers. Pearson's correlations and p-values for each association are shown.
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