Mitochondrial biogenesis during cellular differentiation

1997 ◽  
Vol 272 (4) ◽  
pp. C1345-C1351 ◽  
Author(s):  
C. D. Moyes ◽  
O. A. Mathieu-Costello ◽  
N. Tsuchiya ◽  
C. Filburn ◽  
R. G. Hansford
Keyword(s):  
Mitochondrial Biogenesis ◽  
Nadh Dehydrogenase ◽  
Citrate Synthase ◽  
C2c12 Cells ◽  
Northern Blots ◽  
Quantitative Ultrastructure ◽  
Mitochondrial Volume ◽  
Hydroxyacyl Coa Dehydrogenase ◽  
Mature Enzyme ◽  
Immortalized Cell

Mitochondrial biogenesis was studied during differentiation of two immortalized cell lines (C2C12, 3T3) with enzyme measurements, Northern blots, and quantitative ultrastructure. Citrate synthase, isocitrate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase (nuclear encoded, mitochondrial matrix location) showed linear, four- to sixfold increases in enzymatic activity in C2C12 cells but increased exponentially in 3T3 cells. Cytochrome oxidase and NADH dehydrogenase (nuclear and mitochondrial encoded, cristae location) increased to a lesser extent and with a pattern dissimilar to the first group. Northern blots and activity of succinate dehydrogenase (cristae location but entirely nuclear encoded) suggested the groupings were based on location of the genes rather than the mature enzyme. However, quantitative electron microscopy and comparisons with adult tissue suggested that mitochondrial ultrastructure can influence the change in cristae enzymes. Cristae surface area per unit mitochondrial volume and per unit cell volume increased much less than did cristae enzymes. Available space on the inner membrane may become limiting and account for some aspects of the pattern of change in electron transport enzymes during differentiation.

High aerobic capacities in the skeletal muscles of pinnipeds: adaptations to diving hypoxia

1999 ◽  
Vol 86 (4) ◽  
pp. 1247-1256 ◽  
Author(s):  
Shane B. Kanatous ◽  
Leonard V. DiMichele ◽  
Daniel F. Cowan ◽  
Randall W. Davis
Keyword(s):  
Skeletal Muscles ◽  
Citrate Synthase ◽  
Volume Density ◽  
Harbor Seals ◽  
Eumetopias Jubatus ◽  
Sea Lions ◽  
Hypoxic Conditions ◽  
Fur Seals ◽  
Mitochondrial Volume ◽  
Hydroxyacyl Coa Dehydrogenase

The objective was to assess the aerobic capacity of skeletal muscles in pinnipeds. Samples of swimming and nonswimming muscles were collected from Steller sea lions ( Eumetopias jubatus, n = 27), Northern fur seals ( Callorhinus ursinus, n = 5), and harbor seals ( Phoca vitulina, n = 37) by using a needle biopsy technique. Samples were either immediately fixed in 2% glutaraldehyde or frozen in liquid nitrogen. The volume density of mitochondria, myoglobin concentration, citrate synthase activity, and β-hydroxyacyl-CoA dehydrogenase was determined for all samples. The swimming muscles of seals had an average total mitochondrial volume density per volume of fiber of 9.7%. The swimming muscles of sea lions and fur seals had average mitochondrial volume densities of 6.2 and 8.8%, respectively. These values were 1.7- to 2.0-fold greater than in the nonswimming muscles. Myoglobin concentration, citrate synthase activity, and β-hydroxyacyl-CoA dehydrogenase were 1.1- to 2.3-fold greater in the swimming vs. nonswimming muscles. The swimming muscles of pinnipeds appear to be adapted for aerobic lipid metabolism under the hypoxic conditions that occur during diving.

Schisandrin Restores the Amyloid β-Induced Impairments on Mitochondrial Function, Energy Metabolism, Biogenesis, and Dynamics in Rat Primary Hippocampal Neurons

Pharmacology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Zhongyuan Piao ◽  
Lin Song ◽  
Lifen Yao ◽  
Limei Zhang ◽  
Yichan Lu
Keyword(s):  
Energy Metabolism ◽  
Cytochrome C ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Hippocampal Neurons ◽  
Citrate Synthase ◽  
Mitochondrial Permeability Transition ◽  
Amyloid Β ◽  
Mitochondrial Functions ◽  
Primary Hippocampal Neurons

Introduction: Schisandrin which is derived from Schisandra chinensis has shown multiple pharmacological effects on various diseases including Alzheimer’s disease (AD). It is demonstrated that mitochondrial dysfunction plays an essential role in the pathogenesis of neurodegenerative disorders. Objective: Our study aims to investigate the effects of schisandrin on mitochondrial functions and metabolisms in primary hippocampal neurons. Methods: In our study, rat primary hippocampal neurons were isolated and treated with indicated dose of amyloid β1–42 (Aβ1–42) oligomer to establish a cell model of AD in vitro. Schisandrin (2 μg/mL) was further subjected to test its effects on mitochondrial function, energy metabolism, mitochondrial biogenesis, and dynamics in the Aβ1–42 oligomer-treated neurons. Results and Conclusions: Our findings indicated that schisandrin significantly alleviated the Aβ1–42 oligomer-induced loss of mitochondrial membrane potential and impaired cytochrome c oxidase activity. Additionally, the opening of mitochondrial permeability transition pore and release of cytochrome c were highly restricted with schisandrin treatment. Alterations in cell viability, ATP production, citrate synthase activity, and the expressions of glycolysis-related enzymes demonstrated the relief of defective energy metabolism in Aβ-treated neurons after the treatment of schisandrin. For mitochondrial biogenesis, elevated expression of peroxisome proliferator-activated receptor γ coactivator along with promoted mitochondrial mass was found in schisandrin-treated cells. The imbalance in the cycle of fusion and fission was also remarkably restored by schisandrin. In summary, this study provides novel mechanisms for the protective effect of schisandrin on mitochondria-related functions.

scholarly journals 145 President Oral Presentation Pick: Prenatal stress increases skeletal muscle mitochondrial volume density and function in yearling Brahman calves

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 120-121
Author(s):  
Chloey P Guy ◽  
Catherine L Wellman ◽  
David G Riley ◽  
Charles R Long ◽  
Ron D Randel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Creatine Kinase ◽  
Muscle Damage ◽  
Prenatal Stress ◽  
Citrate Synthase ◽  
Volume Density ◽  
Assembly Factor ◽  
Mitochondrial Volume ◽  
Mitochondrial Volume Density ◽  
And Function

Abstract We previously determined that prenatal stress (PNS) differentially affected methylation of DNA from leukocytes of 28-d-old calves. Specifically, COX14 (cytochrome c oxidase (COX) assembly factor) and CKMT1B (mitochondrial creatine kinase U-type) were hypomethylated and COA5 (COX assembly factor 5), COX5A (COX subunit 5A), NRF1 (nuclear respiratory factor 1), and GSST1 (glutathione S-transferase theta-1) were hypermethylated in PNS compared to non-PNS calves (P ≤ 0.05). Our current objective was to test the hypothesis that PNS exhibit impaired mitochondrial function and greater oxidative stress than non-PNS calves. Blood and longissimus dorsi muscle samples were collected from yearling Brahman calves whose mothers were stressed by 2 h transportation at 60, 80, 100, 120, and 140 days of gestation (PNS; 8 bulls, 6 heifers) and non-PNS calves (4 bulls, 6 heifers). Serum was evaluated for the stress hormone, cortisol, and muscle damage marker, creatine kinase; muscle was analyzed for mitochondrial volume density and function by citrate synthase (CS) and COX activities, respectively, concentration of malondialdehyde, a lipid peroxidation marker, and activity of the antioxidant, superoxide dismutase (SOD). Data were analyzed using mixed linear models with treatment and sex as fixed effects. Serum cortisol was numerically higher in PNS than non-PNS calves but was not statistically different. Muscle CS and COX activities relative to protein were greater in PNS than non-PNS calves (P ≤ 0.03), but COX relative to CS activity was similar between groups. Activity of COX was greater in bulls than heifers (P = 0.03), but no other measure was affected by sex. All other measures were unaffected by PNS. Prenatal stress did not affect markers of muscle damage and oxidative stress in yearling Brahman calves at rest but mitochondrial volume density and function were greater in PNS calves. Acute stressors induce oxidative stress, so implications of differences in mitochondria in PNS calves following a stressor should be investigated.

scholarly journals PSIX-33 Docosahexaenoic Acid (DHA) but not Eicosapentaenoic Acid (EPA) induces the trans-differentiation of C2C12 into white-like adipocytes phenotype

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 309-310
Author(s):  
Yan Huang ◽  
Saeed Ghnaimawi ◽  
Yongjie Wang ◽  
Shilei Zhang ◽  
Jamie Baum
Keyword(s):  
Mitochondrial Biogenesis ◽  
Cultured Cells ◽  
Adipogenic Differentiation ◽  
The Body ◽  
C2c12 Cells ◽  
Brown Adipocyte ◽  
Marker Genes ◽  
Induction Medium ◽  
Spare Capacity ◽  
Epa And Dha

Abstract Muscle-derived stem cells (MDSCs, or myoblasts) play an important role in myotubes regeneration. However, these cells can differentiate into adipocytes once exposed to EPA and DHA, which are highly suggested during pregnancy. The objective of this study aims at determining the effect of isolated EPA and DHA on C2C12 cells undergoing white and brown adipogenic differentiation. Confluent cultured cells were treated with white and brown adipocyte induction medium (WIM and BIM respectively) with 50µM EPA and 50µM DHA separately. DHA treated groups differentiated into white-like adipocyte by down-regulating the expression of myogenic genes such as MyoD, MyoG, and Mrf4; but promoted white adipocyte marker genes(P < 0.05). Moreover, cells treated with WIM and DHA exhibited a decrease in mitochondrial biogenesis through suppressing PGC1a and TFAM expression (P < 0.05). Also, DHA promoted the expression of lipolysis regulating genes. DHA impaired C2C12 cells browning through reducing the mitochondrial biogenesis by significantly suppressing the expression of COX7a1, PGC1a, and UCP3 genes (P < 0.05). DHA treated groups showed an increased accumulation of lipid droplets and suppressed maximal mitochondrial respiration and spare capacity. EPA treatment reduced myogenesis regulating genes (P < 0.05) but did not affect adipogenic genes (P >0.05). Likewise, EPA suppressed the expression of WAT signature genes (P < 0.05), indicating its antagonism to DHA. EPA and WIM treatment suppressed the expression of TFAM and PGC1a, but did not affect PGC1a protein level. Although mitochondrial biogenic gene expression was reduced in EPA and BIDM treated group, no changes in mitochondrial function were observed. EPA supplementation did not affect the differential route of C2C12 into brown adipocytes. To conclude, EPA and DHA may similarly affect the integrity of muscle tissue, but DHA is a potent adipogenic and lipogenic factor that can change the metabolic profile of the body by increasing intramuscular fat.

Curcumin induces mitochondrial biogenesis by increasing cAMP levels via PDE4A inhibition in skeletal muscle

2021 ◽  
pp. 1-34
Author(s):  
Hamidie Ronald D Ray ◽  
Tsubasa Shibaguchi ◽  
Tatsuya Yamada ◽  
Rikuhide Koma ◽  
Rie Ishizawa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Respiration ◽  
Citrate Synthase ◽  
Signalling Pathway ◽  
Curcumin Treatment ◽  
Camp Content ◽  
Signalling Molecules ◽  
Camp Levels

Abstract Background: Previous research has suggested that curcumin potentially induces mitochondrial biogenesis in skeletal muscle via increasing cAMP levels. However, the regulatory mechanisms for this phenomenon remain unknown. The purpose of the present study was to clarify the mechanism by which curcumin activates cAMP-related signalling pathways that upregulate mitochondrial biogenesis and respiration in skeletal muscle. Methods: The effect of curcumin treatment (i.p., 100 mg/kg-BW/day for 28 days) on mitochondrial biogenesis was determined in rats. The effects of curcumin and exercise (swimming for 2 h/day for 3 days) on the cAMP signalling pathway were determined in the absence and presence of phosphodiesterase (PDE) or protein kinase A (PKA) inhibitors. Mitochondrial respiration, citrate synthase (CS) activity, cAMP content, and protein expression of cAMP/PKA signalling molecules were analysed. Results: Curcumin administration increased COX-IV protein expression, and CS and complex I activity, consistent with the induction of mitochondrial biogenesis by curcumin. Mitochondrial respiration was not altered by curcumin treatment. Curcumin and PDE inhibition tended to increase cAMP levels with or without exercise. In addition, exercise increased the phosphorylation of PDE4A, whereas curcumin treatment strongly inhibited PDE4A phosphorylation regardless of exercise. Furthermore, curcumin promoted AMPK phosphorylation and PGC-1α deacetylation. Inhibition of PKA abolished the phosphorylation of AMPK. Conclusion: The present results suggest that curcumin increases cAMP levels via inhibition of PDE4A phosphorylation, which induces mitochondrial biogenesis through a cAMP/PKA/AMPK signalling pathway. Our data also suggest the possibility that curcumin utilizes a regulatory mechanism for mitochondrial biogenesis that is distinct from the exercise-induced mechanism in skeletal muscle.

241 Skeletal Muscle Mitochondrial Capacities Are Impacted by Breed and Temperament in Young Angus and Brahman Steers

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 127-127
Author(s):  
Chloey P Guy ◽  
Lauren T Wesolowski ◽  
Audrey L Earnhardt ◽  
Dustin Law ◽  
Don A Neuendorff ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fixed Effects ◽  
Linear Models ◽  
Citrate Synthase ◽  
Volume Density ◽  
Skeletal Muscle Mitochondria ◽  
Mitochondrial Volume ◽  
Mitochondrial Volume Density ◽  
Brahman Steers ◽  
The Impact

Abstract Temperament impacts skeletal muscle mitochondria in Brahman heifers, but this has not been investigated in steers or between cattle breeds. We hypothesized mitochondrial measures would be greater in Angus than Brahman, temperamental than calm steers, and the trapezius (TRAP) than the longissimus thoracis (LT) muscle. Samples from calm (n = 13 per breed), intermediate (n = 12 per breed), and temperamental (n=13 per breed) Angus and Brahman steers (mean±SD 10.0±0.8 mo) were evaluated for mitochondrial enzyme activities via colorimetry. Calm and temperamental LT samples were evaluated for oxidative phosphorylation (P) and electron transfer (E) capacities by high-resolution respirometry. Data were analyzed using linear models with fixed effects of breed, muscle, temperament, and all interactions. Brahman tended to have greater mitochondrial volume density (citrate synthase activity; CS) than Angus (P = 0.08), while intrinsic (relative to CS) mitochondrial function (cytochrome c oxidase activity) was greater in Angus than Brahman (P = 0.001) and greater in TRAP than LT (P = 0.008). Angus exhibited greater integrative (per mg tissue) and intrinsic P with complex I (PCI), P with complexes I+II (PCI+II), maximum noncoupled E, and E with complex II (ECII; P ≤ 0.04) and tended to have greater intrinsic leak (P = 0.1) than Brahman. Contribution of PCI to total E was greater in Angus than Brahman (P = 0.01), while contribution of ECII to total E was greater in Brahman than Angus (P = 0.05). A trend for the interaction of breed and temperament (P = 0.07) indicated calm Angus had the greatest intrinsic ECII (P ≤ 0.03) while intrinsic ECII was similar between temperamental Angus and calm and temperamental Brahman. Integrative PCI+II and ECII, and the contribution of PCI and PCI+II to overall E tended to be greater in temperamental than calm steers (P ≤ 0.09), while intrinsic ECII tended to be greater in calm than temperamental steers (P = 0.07). The impact of these mitochondrial differences on meat quality measures remains to be determined.

Influence of training on skeletal muscle enzymatic adaptations in normal and diabetic rats

1985 ◽  
Vol 249 (4) ◽  
pp. E360-E365 ◽  
Author(s):  
E. G. Noble ◽  
C. D. Ianuzzo
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Citrate Synthase ◽  
Diabetic Rats ◽  
Muscle Fiber Types ◽  
Fiber Types ◽  
Marker Enzymes ◽  
Oxidative Potential ◽  
Hydroxyacyl Coa Dehydrogenase ◽  
Fast Twitch

Muscle homogenates representing slow-twitch oxidative, fast-twitch oxidative-glycolytic, fast-twitch glycolytic, and mixed fiber types were prepared from normal, diabetic, and insulin-treated diabetic rats. Diabetes was induced by injection of 80 mg . kg-1 of streptozotocin. The activities of citrate synthase, succinate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase were employed as markers of oxidative potential, whereas phosphorylase, hexokinase, and phosphofructokinase activities were used as an indication of glycolytic capacity. Diabetes was associated with a general decrement in the activity of oxidative marker enzymes for all fiber types except the fast-twitch glycolytic fiber. In contrast, the fast-twitch glycolytic fibers demonstrated the greatest decline in glycolytic enzymatic activity. Insulin-treated animals, either trained or untrained, exhibited enzyme activities similar to their normal counterparts. Exercise training of diabetic rats mimicked the effect of insulin treatment and caused a near normalization of the activity of the marker enzymes. These findings suggest that the enzymatic potential of all skeletal muscle fiber types of diabetic rats may be normalized by exercise training even in the absence of significant amounts of insulin.

Abstract 438: Hydrogen Sulfide Promotes Mitochondrial Biogenesis Through the Regulation of AMP-activated Protein Kinase

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Yuuki Shimizu ◽  
Rohini Polavarapu ◽  
John Calvert
Keyword(s):  
Hydrogen Sulfide ◽  
Mitochondrial Biogenesis ◽  
Target Genes ◽  
Nuclear Dna ◽  
Citrate Synthase ◽  
Serine Phosphorylation ◽  
Signaling Cascade ◽  
Disease States ◽  
Upstream Kinase ◽  
High Concentrations

Background: Hydrogen sulfide (H 2 S) possesses numerous cellular actions that account for its cardioprotective effects. A mechanism of particular interest is its effects on the mitochondria. At low concentrations, H 2 S donates electrons to the electron transport chain, whereas at high concentrations it inhibits mitochondrial respiration. H 2 S therapy improves mitochondrial function and prevents the loss of mitochondria following the onset of myocardial ischemia. However, it is not known if these improvements are associated with simply a reduction in injury or if mitochondrial biogenesis is involved. Therefore, the purpose of this study was to determine if H 2 S regulates/induces mitochondrial biogenesis in the heart. Methods and Results: C57BL/6J mice (8 weeks of age) were given an orally active H 2 S donor (SG-1002; 20 mg/kg/day) in their chow for 4 weeks. For these studies we focused our analysis on an AMPK-PGC1α signaling cascade. SG-1002 significantly increased the phosphorylation of AMPK, the serine phosphorylation of PGC1α, and increased the nuclear localization of PGC1α. This was associated with an increase in the gene expression of PGC1α target genes associated with mitochondrial biogenesis, an increase in mitochondrial to nuclear DNA ratios and an increase in citrate synthase activity. SG-1002 failed to elicit these changes in AMPK deficient mice. Therefore, we sought to determine how SG-1002 activated AMPK. SG-1002 did not alter the phosphorylation of LKB1, an upstream kinase of AMPK, and did not alter the levels of AMP (activator of AMPK). SG-1002 did not alter the expression of protein phosphatase 2A (PP2A; dephosphorylates AMPK), but it did significantly decrease the activity of PP2A). This decrease was accompanied by an increase in the sulfhydration of PP2A, suggesting that this modification is inhibitory. Conclusion: These data suggest that H 2 S augments mitochondrial biogenesis in the heart via an AMPK-PGC1α signaling cascade. This is important because mitochondrial abnormalities are associated with a number of disease states (diabetes and heart failure) where H 2 S levels are decreased. Therefore, strategies aimed at increasing H 2 S levels could potentially induce the generation of new, healthy mitochondria.

Mitochondrial biogenesis in striated muscles: rapid induction of citrate synthase mRNA by nerve stimulation

1991 ◽  
Vol 260 (2) ◽  
pp. C266-C270 ◽  
Author(s):  
B. H. Annex ◽  
W. E. Kraus ◽  
G. L. Dohm ◽  
R. S. Williams
Keyword(s):  
Mitochondrial Biogenesis ◽  
Nerve Stimulation ◽  
Time Course ◽  
Citrate Synthase ◽  
Contractile Activity ◽  
Cdna Probe ◽  
Nuclear Gene ◽  
Mitochondrial Genes ◽  
Adult Rabbit ◽  
Mitochondrial Rna

Tonic contractile activity induces mitochondrial biogenesis in mammalian skeletal muscles, necessitating regulation of both nuclear and mitochondrial genes encoding mitochondrial proteins. In this study we compared the time course of induction of citrate synthase (CS) mRNA, a nuclear gene product, to that of genes encoded by mitochondrial DNA during the adaptive response to indirect nerve stimulation in tibialis anterior muscles of adult rabbits. A CS cDNA probe was prepared from a rabbit heart cDNA library by the polymerase chain reaction using synthetic oligonucleotide primers based on the published sequence of the porcine gene. This cDNA probe hybridized to a single band on Northern blots of total or polyadenylated RNA from adult rabbit tissues. Nerve stimulation for 3 days increased the abundance of CS mRNA relative to total cellular RNA by 2.3 +/- 0.2-fold (mean +/- SE, n = 8; P less than 0.01). In contrast, CS enzyme activity and mitochondrial RNA transcripts were not significantly increased at this time point. However, when nerve stimulation was continued for 21 days, the increases in CS mRNA and mitochondrial RNAs were similar. These results support the hypothesis that genetic signaling mechanisms triggered by neural input are sensed initially within the nucleus and that expression of mitochondrial genes is regulated as a secondary event.

Changes in the metabolic profile of equine muscle from birth through 1 yr of age

1990 ◽  
Vol 68 (4) ◽  
pp. 1399-1404 ◽  
Author(s):  
K. H. Kline ◽  
P. J. Bechtel
Keyword(s):  
Lactate Dehydrogenase ◽  
Citrate Synthase ◽  
Fiber Type ◽  
Gluteus Medius ◽  
Fiber Types ◽  
Superficial Fascia ◽  
Muscle Enzyme ◽  
Lactate Dehydrogenase Activity ◽  
Hydroxyacyl Coa Dehydrogenase ◽  
Fast Twitch

The purpose of this study was to investigate metabolic changes in equine muscle from birth to 1 yr of age. Duplicate biopsies from the middle portion of the gluteus medius were obtained from a depth of 2 cm beneath the superficial fascia at 1 day, 7 days, 1 mo, 3 mo, 6 mo, and 1 yr of age in 11 quarter horses and at 1 day, 3 mo, 6 mo, and 1 yr of age in 5 Standardbreds. Muscle enzyme activities determined were citrate synthase, 3-hydroxyacyl-CoA dehydrogenase, phosphorylase, and lactate dehydrogenase. Percent fast-twitch, fast-twitch high oxidative, and slow-twitch oxidative fiber types were determined using succinate dehydrogenase and myosin adenosinetriphosphatase (pH 9.4) histochemical stains. Histochemically determined muscle fiber-type percents did not change dramatically with increasing age. However, lactate dehydrogenase activity increased threefold in quarter horses and twofold in Standardbreds, and phosphorylase activity increased sixfold in quarter horses and sevenfold in Standardbreds from 1 day to 6 mo of age. Citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activities decreased during the first 3 mo of age in quarter horses.

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