scholarly journals Mitochondrial oxygen consumption in early postmortem permeabilized skeletal muscle fibers is influenced by cattle breed

2020 ◽  
Vol 98 (3) ◽  
Author(s):  
Patricia M Ramos ◽  
Chengcheng Li ◽  
Mauricio A Elzo ◽  
Stephanie E Wohlgemuth ◽  
Tracy L Scheffler
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Oxidative Phosphorylation ◽  
Heat Tolerance ◽  
Complex I ◽  
Citrate Synthase ◽  
Ex Vivo ◽  
Muscle Fibers ◽  
Cattle Breed ◽  
Early Postmortem

Abstract Functional properties and integrity of skeletal muscle mitochondria (mt) during the early postmortem period may influence energy metabolism and pH decline, thereby impacting meat quality development. Angus typically produce more tender beef than Brahman, a Bos indicus breed known for heat tolerance. Thus, our objectives were to compare mt respiratory function in muscle collected early postmortem (1 h) from Angus and Brahman steers (n = 26); and to evaluate the effect of normal and elevated temperature on mt function ex vivo. We measured mt oxygen consumption rate (OCR) in fresh-permeabilized muscle fibers from Longissimus lumborum (LL) at 2 temperatures (38.5 and 40.0 °C) and determined citrate synthase (CS) activity and expression of several mt proteins. The main effects of breed, temperature, and their interaction were tested for mt respiration, and breed effect was tested for CS activity and protein expression. Breed, but not temperature (P > 0.40), influenced mt OCR (per tissue weight), with Brahman exhibiting greater complex I+II-mediated oxidative phosphorylation capacity (P = 0.05). Complex I- and complex II-mediated OCR also tended to be greater in Brahman (P = 0.07 and P = 0.09, respectively). Activity of CS was higher in LL from Brahman compared to Angus (P = 0.05). Expression of specific mt proteins did not differ between breeds, except for higher expression of adenosine triphosphate (ATP) synthase subunit 5 alpha in Brahman muscle (P = 0.04). Coupling control ratio differed between breeds (P = 0.05), revealing greater coupling between oxygen consumption and phosphorylation in Brahman. Our data demonstrate that both Angus and Brahman mt retained functional capacity and integrity 1-h postmortem; greater oxidative phosphorylation capacity and coupling in Brahman mt could be related to heat tolerance and impact early postmortem metabolism.

scholarly journals PSV-25 Mitochondrial function of skeletal muscle early postmortem is influenced by cattle breed and temperature

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 334-334
Author(s):  
Patricia Ramos ◽  
Chengcheng Li ◽  
Mauricio Elzo ◽  
Stephanie Wohlgemuth ◽  
Tracy Scheffler
Keyword(s):  
Skeletal Muscle ◽  
Meat Quality ◽  
Heat Tolerance ◽  
Mitochondrial Function ◽  
Complex I ◽  
Citrate Synthase ◽  
Bos Taurus ◽  
Cattle Breed ◽  
Longissimus Lumborum ◽  
Early Postmortem

Abstract Functional properties and integrity of skeletal muscle mitochondria during the early postmortem period may influence development of meat quality traits, such as tenderness. Angus typically produce more tender beef than Brahman, a Bos taurus indicus subspecies known for heat tolerance. Thus, our objectives were to assess mitochondrial function in muscle collected early postmortem from Angus and Brahman cattle; and to evaluate the effect of normal and elevated temperature on mitochondria function. Longissimus lumborum was collected at 1h postmortem from Angus and Brahman steers, and high resolution respirometry was used to assess mitochondrial function in permeabilized muscle fibers at two temperatures (38.5 and 40.0°C). The main effects of breed, temperature, and their interaction were tested. On a tissue weight basis, parameters of respiratory function were not influenced by breed or temperature, though Brahman exhibited numerically greater values for respiration supported by complex I, complex I+II, and complex II substrates. Citrate synthase activity, a marker of mitochondria content, was affected by breed (P = 0.049). Consequently, oxygen consumption rate (OCR) data were normalized to citrate synthase activity. After normalization for mitochondrial content, the overall mitochondria OCR pattern changed, revealing differences among breeds for proton leak respiration (P = 0.045), as well as a persistent interaction effect primarily related to reduced OCR in mitochondria from Brahman at 40.0°C. In addition, the ratio of OCR for leak relative to complex I+II phosphorylation was lower in Brahman, evidencing greater coupling. However, mean coupling ratios for both Angus and Brahman support that respiration and phosphorylation were well-coupled for both breeds even at 1h postmortem. Thus, mitochondria retain functional capacity and integrity at 1h postmortem; and mitochondria properties may be related to differences in heat tolerance and meat quality development between cattle subspecies.

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 Cell-Permeable Succinate Rescues Mitochondrial Respiration in Cellular Models of Statin Toxicity

2021 ◽  
Vol 22 (1) ◽  
pp. 424
Author(s):  
Vlad F. Avram ◽  
Imen Chamkha ◽  
Eleonor Åsander-Frostner ◽  
Johannes K. Ehinger ◽  
Romulus Z. Timar ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Respiration ◽  
Complex I ◽  
Ex Vivo ◽  
Coupling Efficiency ◽  
Human Platelets ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Cellular Models

Statins are the cornerstone of lipid-lowering therapy. Although generally well tolerated, statin-associated muscle symptoms (SAMS) represent the main reason for treatment discontinuation. Mitochondrial dysfunction of complex I has been implicated in the pathophysiology of SAMS. The present study proposed to assess the concentration-dependent ex vivo effects of three statins on mitochondrial respiration in viable human platelets and to investigate whether a cell-permeable prodrug of succinate (complex II substrate) can compensate for statin-induced mitochondrial dysfunction. Mitochondrial respiration was assessed by high-resolution respirometry in human platelets, acutely exposed to statins in the presence/absence of the prodrug NV118. Statins concentration-dependently inhibited mitochondrial respiration in both intact and permeabilized cells. Further, statins caused an increase in non-ATP generating oxygen consumption (uncoupling), severely limiting the OXPHOS coupling efficiency, a measure of the ATP generating capacity. Cerivastatin (commercially withdrawn due to muscle toxicity) displayed a similar inhibitory capacity compared with the widely prescribed and tolerable atorvastatin, but did not elicit direct complex I inhibition. NV118 increased succinate-supported mitochondrial oxygen consumption in atorvastatin/cerivastatin-exposed platelets leading to normalization of coupled (ATP generating) respiration. The results acquired in isolated human platelets were validated in a limited set of experiments using atorvastatin in HepG2 cells, reinforcing the generalizability of the findings.

scholarly journals Cardiovascular and skeletal muscle health with lifelong exercise

2018 ◽  
Vol 125 (5) ◽  
pp. 1636-1645 ◽  
Author(s):  
Kevin J. Gries ◽  
Ulrika Raue ◽  
Ryan K. Perkins ◽  
Kaleen M. Lavin ◽  
Brittany S. Overstreet ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Aerobic Exercise ◽  
Muscle Biopsy ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Metabolic Phenotype ◽  
Vastus Lateralis Muscle ◽  
Metabolic Fitness ◽  
Lifelong Exercise

The purpose of this study was to examine the effects of aerobic lifelong exercise (LLE) on maximum oxygen consumption (V̇o2max) and skeletal muscle metabolic fitness in trained women ( n = 7, 72 ± 2 yr) and men ( n = 21, 74 ± 1 yr) and compare them to old, healthy nonexercisers (OH; women: n = 10, 75 ± 1 yr; men: n = 10, 75 ± 1 yr) and young exercisers (YE; women: n = 10, 25 ± 1 yr; men: n = 10, 25 ± 1 yr). LLE men were further subdivided based on intensity of lifelong exercise and competitive status into performance (LLE-P, n = 14) and fitness (LLE-F, n = 7). On average, LLE exercised 5 day/wk for 7 h/wk over the past 52 ± 1 yr. Each subject performed a maximal cycle test to assess V̇o2maxand had a vastus lateralis muscle biopsy to examine capillarization and metabolic enzymes [citrate synthase, β-hydroxyacyl-CoA dehydrogenase (β-HAD), and glycogen phosphorylase]. V̇o2maxhad a hierarchical pattern (YE > LLE > OH, P < 0.05) for women (44 ± 2 > 26 ± 2 > 18 ± 1 ml·kg−1·min−1) and men (53 ± 3 > 34 ± 1 > 22 ± 1 ml·kg−1·min−1) and was greater ( P < 0.05) in LLE-P (38 ± 1 ml·kg−1·min−1) than LLE-F (27 ± 2 ml·kg−1·min−1). LLE men regardless of intensity and women had similar capillarization and aerobic enzyme activity (citrate synthase and β-HAD) as YE, which were 20%–90% greater ( P < 0.05) than OH. In summary, these data show a substantial V̇o2maxbenefit with LLE that tracked similarly between the sexes, with further enhancement in performance-trained men. For skeletal muscle, 50+ years of aerobic exercise fully preserved capillarization and aerobic enzymes, regardless of intensity. These data suggest that skeletal muscle metabolic fitness may be easier to maintain with lifelong aerobic exercise than more central aspects of the cardiovascular system.NEW & NOTEWORTHY Lifelong exercise (LLE) is a relatively new and evolving area of study with information especially limited in women and individuals with varying exercise intensity habits. These data show a substantial maximal oxygen consumption benefit with LLE that tracked similarly between the sexes. Our findings contribute to the very limited skeletal muscle biopsy data from LLE women (>70 yr), and similar to men, revealed a preserved metabolic phenotype comparable to young exercisers.

Abstract 16339: Mitochondrial Function in Animal and Novel Human Disease Models of Tachycardiomyopathy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Michael G Paulus ◽  
Kathrin Renner ◽  
Steffen Pabel ◽  
Gabriela Pietrzyk ◽  
Andreas Luchner ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Human Disease ◽  
Citrate Synthase ◽  
Ex Vivo ◽  
Pacemaker Implantation ◽  
Induced Pluripotent Stem Cell ◽  
Cardiomyocyte Hypertrophy ◽  
Ex Vivo Model ◽  
Ablation Therapy

Introduction: Clinical significance of tachycardiomyopathy (TCM) increased with trials on catheter ablation therapy. Myocardial biopsies from patients show disturbed mitochondrial architecture. Hypothesis: TCM involves mitochondrial dysfunction. Methods: First, TCM was investigated in an animal model: pacemaker implantation in 7 rabbits was followed by tachypacing for 30 days (TCM), 7 animals served as sham-operated controls (SHAM). Second, results of the animal study were evaluated for their translational perspective for human disease using a novel model of induced pluripotent stem cell-derived cardiomyocytes (iPS-CM), derived from 4 healthy donors. IPS-CM were paced with 120 bpm (TACH) or 60 bpm (CTRL) for 7 days in vitro. Targeted transcriptomics, high-resolution respirometry and flow cytometry (MitoSOX Red) were performed. To account for variations between cell differentiations, experiments on iPS-CM were carried out in a paired design. Results: TCM showed LV dilatation and dysfunction (ΔLVEDD +5.3±0.2mm; ΔFS -19±8%; TCM-SHAM; p<0.001). Histological findings resembled human disease entailing cardiomyocyte hypertrophy (CSA 519±32μm 2 vs. 413±21μm 2 , p<0.01) without fibrosis (hydroxyproline content, p=0.52). Mitochondrial transcriptome of TCM was characterized by downregulation of 10 antioxidative enzymes (e.g. GPX3, fold change (FC) 0.4; TCM/SHAM; p<0.05) as well as mitochondrial carriers, including ADP/ATP- and NADH-shuttling (SLC25A4, FC 0.7; SLC25A12, FC 0.8; p<0.01). As transcriptomics implied impaired substrate import, respirometry was performed in whole tissue. In support of our findings on the transcriptome level, mitochondrial oxidative phosphorylation capacity decreased in TCM (133±13 vs. 170±16 pmol·O 2 ·s -1 ·mg -1 ·tissue, p<0.05). Similarly, oxidative phosphorylation was reduced in iPS-CM (995±738 vs. 1838±901 pmolO 2 ·s -1 ·IU -1 citrate synthase activity, TACH vs. CTRL, p<0.01). Concurrently, tachypacing increased mitochondrial superoxide emission in iPS-CM (MFI 491±206 vs. 301±119, p<0.05). Conclusions: Persistent tachycardia alters two mitochondrial key functions in an animal and a novel human ex vivo model: oxidative phosphorylation capacity is reduced, while superoxide emission increases.

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 &lt; 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 &lt; 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 Adaptations in Mitochondrial Enzymatic Activity Occurs Independent of Genomic Dosage in Response to Aerobic Exercise Training and Deconditioning in Human Skeletal Muscle

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 237 ◽  
Author(s):  
Andreas Fritzen ◽  
Frank Thøgersen ◽  
Kasper Thybo ◽  
Christoffer Vissing ◽  
Thomas Krag ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Enzymatic Activity ◽  
Endurance Exercise ◽  
Complex I ◽  
Citrate Synthase ◽  
Knee Extensor ◽  
Mitochondrial Complex ◽  
Membrane Markers ◽  
Endurance Exercise Training

Mitochondrial DNA (mtDNA) replication is thought to be an integral part of exercise-training-induced mitochondrial adaptations. Thus, mtDNA level is often used as an index of mitochondrial adaptations in training studies. We investigated the hypothesis that endurance exercise training-induced mitochondrial enzymatic changes are independent of genomic dosage by studying mtDNA content in skeletal muscle in response to six weeks of knee-extensor exercise training followed by four weeks of deconditioning in one leg, comparing results to the contralateral untrained leg, in 10 healthy, untrained male volunteers. Findings were compared to citrate synthase activity, mitochondrial complex activities, and content of mitochondrial membrane markers (porin and cardiolipin). One-legged knee-extensor exercise increased endurance performance by 120%, which was accompanied by increases in power output and peak oxygen uptake of 49% and 33%, respectively (p < 0.01). Citrate synthase and mitochondrial respiratory chain complex I–IV activities were increased by 51% and 46–61%, respectively, in the trained leg (p < 0.001). Despite a substantial training-induced increase in mitochondrial activity of TCA and ETC enzymes, there was no change in mtDNA and mitochondrial inner and outer membrane markers (i.e. cardiolipin and porin). Conversely, deconditioning reduced endurance capacity by 41%, muscle citrate synthase activity by 32%, and mitochondrial complex I–IV activities by 29–36% (p < 0.05), without any change in mtDNA and porin and cardiolipin content in the previously trained leg. The findings demonstrate that the adaptations in mitochondrial enzymatic activity after aerobic endurance exercise training and the opposite effects of deconditioning are independent of changes in the number of mitochondrial genomes, and likely relate to changes in the rate of transcription of mtDNA.

scholarly journals RAPID COMMUNICATION: Differential skeletal muscle mitochondrial characteristics of weanling racing-bred horses1

2019 ◽  
Vol 97 (8) ◽  
pp. 3193-3198 ◽  
Author(s):  
Christine M Latham ◽  
Clara K Fenger ◽  
Sarah H White
Keyword(s):  
Skeletal Muscle ◽  
Electron Transport ◽  
Transport System ◽  
Complex I ◽  
Management Practices ◽  
Citrate Synthase ◽  
Fiber Type ◽  
Gluteus Medius ◽  
Electron Transport System ◽  
Mitochondrial Density

Abstract Responses of equine skeletal muscle characteristics to growth and training have been shown to differ between breeds. These differential responses may arise in part because muscle fiber type and mitochondrial density differ between breeds, even in untrained racing-bred horses. However, it is not known when these breed-specific differences manifest. To test the hypothesis that weanling Standardbreds (SB) and Thoroughbreds (TB) would have higher mitochondrial measures than Quarter Horses (QH), gluteus medius samples were collected from SB (mean ± SD; 6.2 ± 1.0 mo; n = 10), TB (6.1 ± 0.5 mo; n = 12), and QH (7.4 ± 0.6 mo; n = 10). Citrate synthase (CS) and cytochrome c oxidase (CCO) activities were assessed as markers of mitochondrial density and function, respectively. Mitochondrial oxidative (P) and electron transport system (E) capacities were assessed by high-resolution respirometry (HRR). Data for CCO and HRR are expressed as integrated (per mg protein and per mg tissue wet weight, respectively) and intrinsic (per unit CS). Data were analyzed using PROC MIXED in SAS v 9.4 with breed as a fixed effect. Mitochondrial density (CS) was higher for SB and TB than QH (P ≤ 0.0007). Mitochondrial function (integrated and intrinsic CCO) was higher in TB and QH than SB (P ≤ 0.01). Integrated CCO was also higher in TB than QH (P &lt; 0.0001). However, SB had higher integrated maximum P (PCI+II) and E (ECI+II) than QH (P ≤ 0.02) and greater integrated and intrinsic complex II-supported E (ECII) than both QH and TB (P ≤ 0.02), whereas TB exhibited higher integrated P with complex I substrates (PCI) than SB and QH (P ≤ 0.003) and higher integrated PCI+II and ECI+II than QH (P ≤ 0.02). In agreement, TB and QH had higher contribution of complex I (CI) to max E than SB (P ≤ 0.001), whereas SB had higher contribution of CII than QH and TB (P ≤ 0.002). Despite having higher mitochondrial density than QH and TB, SB showed lower CCO activity and differences in contribution of complexes to oxidative and electron transport system capacities. Breed differences in mitochondrial parameters are present early in life and should be considered when developing feeding, training, medication, and management practices.

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