Exogenous coenzyme Q (CoQ) fails to increase CoQ in skeletal muscle of two patients with mitochondrial myopathies

Abstract Background: Propofol is a short-acting intravenous anesthetic agent. In rare conditions, a life-threatening complication known as propofol infusion syndrome can occur. The pathophysiologic mechanism is still unknown. Some studies suggested that propofol acts as uncoupling agent, others suggested that it inhibits complex I or complex IV, or causes increased oxidation of cytochrome c and cytochrome aa3, or inhibits mitochondrial fatty acid metabolism. Although the exact site of interaction is not known, most hypotheses point to the direction of the mitochondria. Methods: Eight rats were ventilated and sedated with propofol up to 20 h. Sequential biopsy specimens were taken from liver and skeletal muscle and used for determination of respiratory chain activities and propofol concentration. Activities were also measured in skeletal muscle from a patient who died of propofol infusion syndrome. Results: In rats, authors detected a decrease in complex II+III activity starting at low tissue concentration of propofol (20 to 25 µM), further declining at higher concentrations. Before starting anesthesia, the complex II+III/citrate synthase activity ratio in liver was 0.46 (0.25) and in skeletal muscle 0.23 (0.05) (mean [SD]). After 20 h of anesthesia, the ratios declined to 0.17 (0.03) and 0.12 (0.02), respectively. When measured individually, the activities of complexes II and III remained normal. Skeletal muscle from one patient taken in the acute phase of propofol infusion syndrome also shows a selective decrease in complex II+III activity (z-score: −2.96). Conclusion: Propofol impedes the electron flow through the respiratory chain and coenzyme Q is the main site of interaction with propofol.

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Exercise and Simvastatin Interaction on Coenzyme Q and Cytochrome Oxidase in Cardiac and Skeletal Muscle

Medicine & Science in Sports & Exercise ◽

10.1249/00005768-200605001-00909 ◽

2006 ◽

Vol 38 (Supplement) ◽

pp. S4

Author(s):

Mary Pat Meaney ◽

Maxi Meissner ◽

Richard A. Willis ◽

Joseph W. Starnes

Keyword(s):

Skeletal Muscle ◽

Cytochrome Oxidase ◽

Coenzyme Q

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Fourier-Transform Infrared Spectroscopy of Skeletal Muscle Tissue: Expanding Biomarkers in Primary Mitochondrial Myopathies

Genes ◽

10.3390/genes11121522 ◽

2020 ◽

Vol 11 (12) ◽

pp. 1522

Author(s):

Jacopo Gervasoni ◽

Aniello Primiano ◽

Federico Marini ◽

Andrea Sabino ◽

Alessandra Biancolillo ◽

...

Keyword(s):

Skeletal Muscle ◽

Fourier Transform ◽

Ftir Spectroscopy ◽

Nuclear Gene ◽

Mitochondrial Diseases ◽

Fourier Transform Infrared ◽

Progressive External Ophthalmoplegia ◽

Mitochondrial Myopathies ◽

Muscle Involvement ◽

Mtdna Deletion

Primary mitochondrial myopathies (PMM) are a group of mitochondrial disorders characterized by a predominant skeletal muscle involvement. The aim of this study was to evaluate whether the biochemical profile determined by Fourier-transform infrared (FTIR) spectroscopic technique would allow to distinguish among patients affected by progressive external ophthalmoplegia (PEO), the most common PMM presentation, oculopharyngeal muscular dystrophy (OPMD), and healthy controls. Thirty-four participants were enrolled in the study. FTIR spectroscopy was found to be a sensitive and specific diagnostic marker for PEO. In particular, FTIR spectroscopy was able to distinguish PEO patients from those affected by OPMD, even in the presence of histological findings similar to mitochondrial myopathy. At the same time, FTIR spectroscopy differentiated single mtDNA deletion and mutations in POLG, the most common nuclear gene associated with mitochondrial diseases, with high sensitivity and specificity. In conclusion, our data suggest that FTIR spectroscopy is a valuable biodiagnostic tool for the differential diagnosis of PEO with a high ability to also distinguish between single mtDNA deletion and mutations in POLG gene based on specific metabolic transitions.

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Prolonged oral coenzyme Q10-β-cyclodextrin supplementation increases skeletal muscle complex I+III activity in young Thoroughbreds

Journal of Applied Animal Nutrition ◽

10.3920/jaan2019.0001 ◽

2020 ◽

Vol 8 (1) ◽

pp. 12-20

Author(s):

M.F. Rooney ◽

C.E. Curley ◽

J. Sweeney ◽

M.E. Griffin ◽

R.K. Porter ◽

...

Keyword(s):

Skeletal Muscle ◽

Complex I ◽

High Performance ◽

Coenzyme Q ◽

Indirect Measurement ◽

Mean Difference ◽

Oral Supplementation ◽

Transport Chain ◽

Muscle Complex ◽

Muscle Biopsies

Coenzyme Q10 (CoQ10) is an essential component of the mitochondrial electron transport chain (ETC). Decreased skeletal muscle CoQ10 content may result in decreased ETC activity and energy production. This study tested the hypotheses that supplementation with oral CoQ10 will increase plasma CoQ10 concentrations and that prolonged supplementation will increase skeletal muscle CoQ10 content in young, healthy untrained Thoroughbreds. Nineteen Thoroughbreds (27.5±9.7 months old; 11 males, eight females) from one farm and maintained on a grass pasture with one grain meal per day were supplemented daily with 1.5 mg/kg body weight of an oral CoQ10-β-cyclodextrin inclusion complex. Whole-blood and skeletal muscle biopsies were collected before (T0) and after (T1) nine weeks of supplementation. Plasma CoQ10 concentrations were determined via high-performance liquid chromatography. Skeletal muscle mitochondrial ETC combined complex I+III enzyme activity (indirect measurement of CoQ10 content) was assessed spectrophotometrically and normalised to mitochondrial abundance. Horses accepted supplementation with no adverse effects. Plasma CoQ10 concentration increased in all horses following supplementation, with mean plasma CoQ10 concentration significantly increasing from T0 to T1 (0.13±0.02 vs 0.25±0.03 μg/ml; mean difference 0.12±0.03; P=0.004). However, variability in absorbance resulted in a 58% response rate (i.e. doubling of T1 above T0 values). The mean skeletal muscle complex I+III activity significantly increased from T0 to T1 (0.36±0.04 vs 0.59±0.05 pmol/min/mg of muscle, mean difference 0.23±0.05; P=0.0004), although T1 values for three out of 19 horses decreased on average by 23% below T0 values. In conclusion, oral supplementation with CoQ10 in the diet of young, healthy untrained Thoroughbreds increased mean plasma CoQ10 concentration by 99% with prolonged daily supplementation increasing mean skeletal muscle complex I+III activity by 65%. Additional research is warranted investigating training and exercise effects on skeletal muscle CoQ10 content in CoQ10 supplemented and un-supplemented Thoroughbreds.

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Mechanisms of the effect of oxidative phosphorylation deficiencies on the skeletal muscle bioenergetic system in patients with mitochondrial myopathies

Journal of Applied Physiology ◽

10.1152/japplphysiol.00196.2021 ◽

2021 ◽

Author(s):

Bernard Korzeniewski

Keyword(s):

Skeletal Muscle ◽

Oxidative Phosphorylation ◽

Muscle Fatigue ◽

Exercise Intolerance ◽

Kinetic Properties ◽

Work Intensity ◽

Mitochondrial Myopathies ◽

Threshold Mechanism ◽

Kinetic Effects ◽

Double Threshold

Simulations carried out using a previously-developed model of the skeletal muscle bioenergetic system, involving the "Pi double-threshold" mechanism of muscle fatigue, lead to the conclusion that a decrease in the oxidative phosphorylation (OXPHOS) activity, caused by mutations in mitochondrial or nuclear DNA, is the main mechanism underlying the changes in the kinetic properties of the system in mitochondrial myopathies (MM). These changes generally involve the very-heavy-exercise-like behavior and exercise termination because of fatigue at low work intensities. In particular, a sufficiently large (at a given work intensity) decrease in OXPHOS activity leads to slowing of the primary phase II of the V̇O2 on-kinetics, decrease in V̇O2max, appearance of the slow component of the V̇O2 on-kinetics, exercise intolerance and lactic acidosis at relatively low power outputs encountered in experimental studies in MM patients. Thus, the "Pi double-threshold" mechanism of muscle fatigue is able to account, at least semi-quantitatively, for various kinetic effects of inborn OXPHOS deficiencies of the skeletal muscle bioenergetic system. Exercise can be potentially lengthened and V̇O2max elevated in MM patients through an increase in peak Pi (Pipeak), at which exercise is terminated because of fatigue. Generally, a mechanism underlying the kinetic effects of OXPHOS deficiencies on the skeletal muscle bioenergetic system in MM is proposed that was absent in the literature.

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