scholarly journals Mitochondrial respiration of complex II is not lower than that of complex I in mouse skeletal muscle

2020 ◽  
Vol 21 ◽  
pp. 100717 ◽  
Author(s):  
Satoshi Maekawa ◽  
Shingo Takada ◽  
Takaaki Furihata ◽  
Arata Fukushima ◽  
Takashi Yokota ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Respiration ◽  
Complex I ◽  
Complex Ii ◽  
Mouse Skeletal Muscle

Effect of hyperthermia and acidosis on equine skeletal muscle mitochondrial oxygen consumption

2020 ◽  
pp. 1-10
Author(s):  
M.S. Davis ◽  
M.R. Fulton ◽  
A. Popken
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Oxidative Phosphorylation ◽  
Muscle Fatigue ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Complex I ◽  
Mitochondrial Oxygen Consumption ◽  
Biochemical Basis ◽  
Complex Ii

The skeletal muscle of exercising horses develops pronounced hyperthermia and acidosis during strenuous or prolonged exercise, with very high tissue temperature and low pH associated with muscle fatigue or damage. The purpose of this study was to evaluate the individual effects of physiologically relevant hyperthermia and acidosis on equine skeletal muscle mitochondrial function, using ex vivo measurement of oxygen consumption to assess the function of different mitochondrial elements. Fresh triceps muscle biopsies from 6 healthy unfit Thoroughbred geldings were permeabilised to permit diffusion of small molecular weight substrates through the sarcolemma and analysed in a high resolution respirometer at 38, 40, 42, and 44 °C, and pH=7.1, 6.5, and 6.1. Oxygen consumption was measured under conditions of non-phosphorylating (leak) respiration and phosphorylating respiration through Complex I and Complex II. Data were analysed using a one-way repeated measures ANOVA and data are expressed as mean ± standard deviation. Leak respiration was ~3-fold higher at 44 °C compared to 38 °C regardless of electron source (Complex I: 22.88±3.05 vs 8.08±1.92 pmol O2/mg/s), P=0.002; Complex II: 79.14±23.72 vs 21.43±11.08 pmol O2/mg/s, P=0.022), resulting in a decrease in efficiency of oxidative phosphorylation. Acidosis had minimal effect on mitochondrial respiration at pH=6.5, but pH=6.1 resulted in a 50% decrease in mitochondrial oxygen consumption. These results suggest that skeletal muscle hyperthermia decreases the efficiency of oxidative phosphorylation through increased leak respiration, thus providing a specific biochemical basis for hyperthermia-induced muscle fatigue. The effect of myocellular acidosis on mitochondrial respiration was minimal under typical levels of acidosis, but atypically severe acidosis can lead to impairment of mitochondrial function.

scholarly journals Dose Response of Endotoxin on Hepatocyte and Muscle Mitochondrial Respiration In Vitro

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Victor Jeger ◽  
Sebastian Brandt ◽  
Francesca Porta ◽  
Stephan M. Jakob ◽  
Jukka Takala ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Membrane Potential ◽  
Mitochondrial Respiration ◽  
Hepg2 Cells ◽  
Human Hepatocytes ◽  
Atp Content ◽  
Muscle Mitochondria ◽  
Complex Ii ◽  
Skeletal Muscle Mitochondria ◽  
Reduced Time

Introduction.Results on mitochondrial dysfunction in sepsis are controversial. We aimed to assess effects of LPS at wide dose and time ranges on hepatocytes and isolated skeletal muscle mitochondria.Methods.Human hepatocellular carcinoma cells (HepG2) were exposed to placebo or LPS (0.1, 1, and 10 μg/mL) for 4, 8, 16, and 24 hours and primary human hepatocytes to 1 μg/mL LPS or placebo (4, 8, and 16 hours). Mitochondria from porcine skeletal muscle samples were exposed to increasing doses of LPS (0.1–100 μg/mg) for 2 and 4 hours. Respiration rates of intact and permeabilized cells and isolated mitochondria were measured by high-resolution respirometry.Results.In HepG2 cells, LPS reduced mitochondrial membrane potential and cellular ATP content but did not modify basal respiration. Stimulated complex II respiration was reduced time-dependently using 1 μg/mL LPS. In primary human hepatocytes, stimulated mitochondrial complex II respiration was reduced time-dependently using 1 μg/mL LPS. In isolated porcine skeletal muscle mitochondria, stimulated respiration decreased at high doses (50 and 100 μg/mL LPS).Conclusion.LPS reduced cellular ATP content of HepG2 cells, most likely as a result of the induced decrease in membrane potential. LPS decreased cellular and isolated mitochondrial respiration in a time-dependent, dose-dependent and complex-dependent manner.

scholarly journals Skeletal Muscle Mitochondrial Respiration Is Elevated in Female Cynomolgus Macaques Fed a Western Compared with a Mediterranean Diet

2019 ◽  
Vol 149 (9) ◽  
pp. 1493-1502 ◽  
Author(s):  
Jenny L Gonzalez-Armenta ◽  
Zhengrong Gao ◽  
Susan E Appt ◽  
Mara Z Vitolins ◽  
Kristofer T Michalson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mediterranean Diet ◽  
Dietary Patterns ◽  
Mitochondrial Respiration ◽  
Complex I ◽  
Western Diet ◽  
Cardiometabolic Health ◽  
Mitochondrial Bioenergetics ◽  
Macronutrient Composition ◽  
Cynomolgus Macaques

ABSTRACT Background Western diets are associated with increased incidences of obesity, hypertension, diabetes, and hypercholesterolemia, whereas Mediterranean diets, richer in polyphenols, monounsaturated fats, fruits, vegetables, poultry, and fish, appear to have cardiometabolic health benefits. Previous work has included population-based studies with limited evidence for causation or animal studies focused on single macro- or micronutrients; therefore, primate animal models provide an opportunity to determine potential mechanisms underlying the effects of dietary patterns on health and disease. Objective The aim of this study was to determine the effects of whole dietary patterns, either a Western or Mediterranean diet, on skeletal muscle mitochondrial bioenergetics in cynomolgus macaques. Methods In this study, 22 adult female cynomolgus macaques (∼11–14 y by dentition) were fed either a Western or Mediterranean diet for 30 mo. The Western diet was designed to mimic the diet of a middle-aged American woman and the Mediterranean diet included key aspects of Mediterranean diets studied in humans, such as plant-based proteins and fat, complex carbohydrates, and fiber. Diets were matched on macronutrient composition (16% protein, 54% carbohydrate, and 31% fat) and cholesterol content. Skeletal muscle was collected for high-resolution respirometry, citrate synthase activity, and western blot measurements. Pearson correlation analysis between respirometry measures and measures of carbohydrate metabolism was also performed. Results We found that consumption of a Western diet resulted in significantly higher mitochondrial respiration with fatty acid oxidation (FAO) (53%), FAO + complex I (52%), complex I + II (31%), max electron transport system (ETS) (31%), and ETS rotenone sensitive (31%) than did consumption of a Mediterranean diet. In addition, measures of respiration in response to fatty acids were significantly and positively correlated with both insulin resistance and plasma insulin concentrations. Conclusions This study highlights the importance of dietary composition in mitochondrial bioenergetics and that diet can influence skeletal muscle mitochondrial respiration independently of other factors such as macronutrient composition.

scholarly journals Skeletal muscle mitochondrial function and exercise capacity are not impaired in mice with knockout of STAT3

2019 ◽  
Vol 127 (4) ◽  
pp. 1117-1127
Author(s):  
Jessica R. Dent ◽  
Byron Hetrick ◽  
Shahriar Tahvilian ◽  
Abha Sathe ◽  
Keenan Greyslak ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Electron Transport ◽  
Complex I ◽  
Physiological Function ◽  
Oxidative Capacity ◽  
Signal Transducer ◽  
Muscle Mitochondria ◽  
Complex Ii ◽  
Skeletal Muscle Mitochondria ◽  
Transcription 3

Signal transducer and activator of transcription 3 (STAT3) was recently found to be localized to mitochondria in a number of tissues and cell types, where it modulates oxidative phosphorylation via interactions with the electron transport proteins, complex I and complex II. Skeletal muscle is densely populated with mitochondria although whether STAT3 contributes to skeletal muscle oxidative capacity is unknown. In the present study, we sought to elucidate the contribution of STAT3 to mitochondrial and skeletal muscle function by studying mice with muscle-specific knockout of STAT3 (mKO). First, we developed a novel flow cytometry-based approach to confirm that STAT3 is present in skeletal muscle mitochondria. However, contrary to findings in other tissue types, complex I and complex II activity and maximal mitochondrial respiratory capacity in skeletal muscle were comparable between mKO mice and floxed/wild-type littermates. Moreover, there were no genotype differences in endurance exercise performance, skeletal muscle force-generating capacity, or the adaptive response of skeletal muscle to voluntary wheel running. Collectively, although we confirm the presence of STAT3 in skeletal muscle mitochondria, our data establish that STAT3 is dispensable for mitochondrial and physiological function in skeletal muscle. NEW & NOTEWORTHY Whether signal transducer and activator of transcription 3 (STAT3) can regulate the activity of complex I and II of the electron transport chain and mitochondrial oxidative capacity in skeletal muscle, as it can in other tissues, is unknown. By using a mouse model lacking STAT3 in muscle, we demonstrate that skeletal muscle mitochondrial and physiological function, both in vivo and ex vivo, is not impacted by the loss of STAT3.

scholarly journals Temperament influences mitochondrial capacity in skeletal muscle from 8 through 18 mo of age in Brahman heifers

2020 ◽  
Vol 98 (10) ◽  
Author(s):  
Randi N Owen ◽  
Christine M Latham ◽  
Charles R Long ◽  
Ronald D Randel ◽  
Thomas H Welsh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Product Quality ◽  
Repeated Measures ◽  
Complex I ◽  
Citrate Synthase ◽  
Serum Cortisol ◽  
System Capacity ◽  
Complex Ii ◽  
Potential Link ◽  
Muscle Groups

Abstract Temperamental cattle tend to yield carcasses of poorer quality, and Brahman cattle are reportedly more temperamental than non-indicus cattle breeds. A potential link between temperament and product quality may be mitochondrial activity. We hypothesized that mitochondrial measures would be greater in temperamental compared with calm heifers and that the relationships between temperament and mitochondria would persist as heifers age. Serum cortisol and skeletal muscle (longissimus thoracis [LT] and trapezius [TRAP]) mitochondrial profiles and antioxidant activities were quantified from the same calm (n = 6) and temperamental (n = 6) Brahman heifers at 8, 12, and 18 mo of age. Data were analyzed using a mixed model ANOVA in SAS (9.4) with repeated measures. Serum cortisol was greater in temperamental compared with calm heifers throughout the study (P = 0.02). Mitochondrial volume density (citrate synthase [CS] activity) increased over time (P < 0.0001) but was similar between temperament and muscle groups. Mitochondrial function (cytochrome c oxidase activity) was greatest in the temperamental LT at 8 mo of age (P ≤ 0.0006), greatest in the temperamental TRAP at 18 mo of age (P ≤ 0.003), and did not differ by temperament at 12 mo of age. Integrative (relative to tissue wet weight) mitochondrial oxidative phosphorylation capacity with complex I substrates (PCI), PCI plus complex II substrate (PCI+II), noncoupled electron transfer system capacity (ECI+II), and E with functional complex II only (ECII) were greater in the TRAP than LT for calm heifers at all ages (P ≤ 0.002), but were similar between muscle groups in temperamental heifers. Overall, calm heifers tended to have greater intrinsic (relative to CS activity) PCI and flux control of PCI+II (P ≤ 0.1) than temperamental heifers, indicating greater utilization of complex I paired with greater coupling efficiency in calm heifers. Within the LT, integrative PCI+II was greater (P = 0.05) and ECI+II tended to be greater (P = 0.06) in temperamental compared with calm heifers. From 8- to 18-mo old, glutathione peroxidase (GPx) activity decreased (P < 0.0001) and superoxide dismutase activity increased (P = 0.02), and both were similar between muscle groups. The activity of GPx was greater in temperamental compared with calm heifers at 8 (P = 0.004) but not at 12 or 18 mo of age. These results detail divergent skeletal muscle mitochondrial characteristics of live Brahman heifers according to temperament, which should be further investigated as a potential link between temperament and product quality.

scholarly journals 108 President Oral Presentation Pick: Select skeletal muscle mitochondrial measures in Thoroughbred weanlings are related to race earnings and sire

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 85-85
Author(s):  
Chloey P Guy ◽  
Christine M Latham ◽  
Randi N Owen ◽  
Ashley L Fowler ◽  
Sarah H White-Springer
Keyword(s):  
Skeletal Muscle ◽  
Complex I ◽  
Fixed Effects ◽  
Linear Models ◽  
Citrate Synthase ◽  
Pearson Correlation ◽  
Gluteus Medius ◽  
Volume Density ◽  
Complex Ii ◽  
And Training

Abstract Quantifiable, cellular differences of individuals are not widely used in breeding and training decisions in the equine industry. Our objective was to determine if mitochondrial parameters in weanling Thoroughbreds were related to sire or lifetime race earnings. We hypothesized that weanling skeletal muscle mitochondrial capacity would be positively correlated with race earnings. Gluteus medius muscle samples were collected from racing-bred Thoroughbred weanlings (n = 139; mean ± SD; 6.0 ± 0.4 mo) from 40 different sires over 3 years at 5 different farms and evaluated for mitochondrial volume density (citrate synthase activity; CS) and function (cytochrome c oxidase activity) by colorimetry, and oxidative (P) and electron transport system (E) capacities by high resolution respirometry; two- and three-year-old race earnings were available for a subset of 13 horses. Data were analyzed using mixed linear models with sire, sex, year of collection, and farm as fixed effects. Correlations between lifetime race earnings and mitochondrial measures were determined using Pearson Correlation Statistics. A main effect of sire was observed for weanling intrinsic (relative to CS activity) P with complex I substrates (P = 0.04) and the contribution of mitochondrial leak to O2 consumption (FCRL; P = 0.04). A trend was observed for the effect of sire on intrinsic mitochondrial leak (P = 0.09). Race earnings were positively correlated with integrated (relative to mg protein) leak (r = 0.7684, P = 0.009) and FCRL (r = 0.7035; P = 0.02). A trend for a negative correlation between E with complex II substrates and race earnings was also observed (r = -0.4775, P = 0.09), No other measures were influenced by sire, nor were correlated with race earnings. Our previous work has indicated a preferential use of complex I in breeds bred for short-duration racing (Thoroughbreds) compared to distance racing breeds (Standardbreds) that relied more heavily on complex II. Mitochondrial measures in weanlings may be utilized to inform future breeding and training decisions in horses.

scholarly journals Skeletal muscle mitochondrial function in polycystic ovarian syndrome

2011 ◽  
Vol 165 (4) ◽  
pp. 631-637 ◽  
Author(s):  
Rasmus Rabøl ◽  
Pernille F Svendsen ◽  
Mette Skovbro ◽  
Robert Boushel ◽  
Peter Schjerling ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
High Resolution ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Complex I ◽  
Polycystic Ovarian Syndrome ◽  
Obese Women ◽  
Mitochondrial Content ◽  
Ovarian Syndrome

ObjectivePolycystic ovarian syndrome (PCOS) is associated with skeletal muscle insulin resistance (IR), which has been linked to decreased mitochondrial function. We measured mitochondrial respiration in lean and obese women with and without PCOS using high-resolution respirometry.MethodsHyperinsulinemic–euglycemic clamps (40 mU/min per m2) and muscle biopsies were performed on 23 women with PCOS (nine lean (body mass index (BMI) <25 kg/m2) and 14 obese (BMI >25 kg/m2)) and 17 age- and weight-matched controls (six lean and 11 obese). Western blotting and high-resolution respirometry was used to determine mitochondrial function.ResultsInsulin sensitivity decreased with PCOS and increasing body weight. Mitochondrial respiration with substrates for complex I and complex I+II were similar in all groups, and PCOS was not associated with a decrease in mitochondrial content as measured by mitochondrial DNA/genomic DNA. We found no correlation between mitochondrial function and indices of insulin sensitivity.ConclusionsIn contrast to previous reports, we found no evidence that skeletal muscle mitochondrial respiration is reduced in skeletal muscle of women with PCOS compared with control subjects. Furthermore, mitochondrial content did not differ between our control and PCOS groups. These results question the causal relationship between reduced mitochondrial function and skeletal muscle IR in PCOS.

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