scholarly journals Sirtuin 1 (SIRT1) Deacetylase Activity Is Not Required for Mitochondrial Biogenesis or Peroxisome Proliferator-activated Receptor-γ Coactivator-1α (PGC-1α) Deacetylation following Endurance Exercise

2011 ◽  
Vol 286 (35) ◽  
pp. 30561-30570 ◽  
Author(s):  
Andrew Philp ◽  
Ai Chen ◽  
Debin Lan ◽  
Gretchen A. Meyer ◽  
Anne N. Murphy ◽  
...  
Keyword(s):  
Endurance Exercise ◽  
Mitochondrial Biogenesis ◽  
Sirtuin 1 ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals The Effect of Diet on Improved Endurance in Male C57BL/6 Mice

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1101 ◽  
Author(s):  
Jin Yu ◽  
Hong Zhu ◽  
Saeid Taheri ◽  
Stephen Perry ◽  
Mark Kindy
Keyword(s):  
Mitochondrial Biogenesis ◽  
Fruits And Vegetables ◽  
Sirtuin 1 ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Mitochondrial Transcription Factor ◽  
Exercise Endurance ◽  
The Impact

The consumption of fruits and vegetables appears to help with maintaining an adequate level of exercise and improves endurance. However, the mechanisms that are involved in this process are not well understood. In the current study, the impact of diets enriched in fruits and vegetables (GrandFusion®) on exercise endurance was examined in a mouse model. GrandFusion (GF) diets increased mitochondrial DNA and enzyme activity, while they also stimulated mitochondrial mRNA synthesis in vivo. GF diets increased both the mRNA expression of factors involved in mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (Tfam), estrogen-related receptor alpha (ERRα), nuclear respiratory factor 1 (NRF-1), cytochrome c oxidase IV (COXIV) and ATP synthase (ATPsyn). Mice treated with GF diets showed an increase in running endurance, rotarod perseverance and grip strength when compared to controls who were on a regular diet. In addition, GF diets increased the protein expression of phosphorylated AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), PGC-1α and peroxisome proliferator-activated receptor delta (PPAR-δ), which was greater than exercise-related changes. Finally, GF reduced the expression of phosphorylated ribosomal protein S6 kinase 1 (p-S6K1) and decreased autophagy. These results demonstrate that GF diets enhance exercise endurance, which is mediated via mitochondrial biogenesis and function.

scholarly journals Effects of Rhizome Extract of Dioscorea batatas and Its Active Compound, Allantoin, on the Regulation of Myoblast Differentiation and Mitochondrial Biogenesis in C2C12 Myotubes

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 2023 ◽  
Author(s):  
Junnan Ma ◽  
Seok Yong Kang ◽  
Xianglong Meng ◽  
An Na Kang ◽  
Jong Hun Park ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Mitochondrial Biogenesis ◽  
Water Extract ◽  
Sirtuin 1 ◽  
Myoblast Differentiation ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dioscorea Batatas

With the aging process, a loss of skeletal muscle mass and dysfunction related to metabolic syndrome is observed in older people. Yams are commonly use in functional foods and medications with various effects. The present study was conducted to investigate the effects of rhizome extract of Dioscorea batatas (Dioscoreae Rhizoma, Chinese yam) and its bioactive compound, allantoin, on myoblast differentiation and mitochondrial biogenesis in skeletal muscle cells. Yams were extracted in water and allantoin was analyzed by high performance liquid chromatography (HPLC). The expression of myosin heavy chain (MyHC) and mitochondrial biogenesis-regulating factors, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), sirtuin-1 (Sirt-1), nuclear respiratory factor-1 (NRF-1) and transcription factor A, mitochondrial (TFAM), and the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) were determined in C2C12 myotubes by reverse transcriptase (RT)-polymerase chain reaction (RT-PCR) or western blot. The glucose levels and total ATP contents were measured by glucose consumption, glucose uptake and ATP assays, respectively. Treatment with yam extract (1 mg/mL) and allantoin (0.2 and 0.5 mM) significantly increased MyHC expression compared with non-treated myotubes. Yam extract and allantoin significantly increased the expression of PGC-1α, Sirt-1, NRF-1 and TFAM, as well as the phosphorylation of AMPK and ACC in C2C12 myotubes. Furthermore, yam extract and allantoin significantly increased glucose uptake levels and ATP contents. Finally, HPLC analysis revealed that the yam water extract contained 1.53% of allantoin. Yam extract and allantoin stimulated myoblast differentiation into myotubes and increased energy production through the upregulation of mitochondrial biogenesis regulators. These findings indicate that yam extract and allantoin can help to prevent skeletal muscle dysfunction through the stimulation of the energy metabolism.

scholarly journals Mild heat stress induces mitochondrial biogenesis in C2C12 myotubes

2012 ◽  
Vol 112 (3) ◽  
pp. 354-361 ◽  
Author(s):  
Chien-Ting Liu ◽  
George A. Brooks
Keyword(s):  
Heat Stress ◽  
Mitochondrial Biogenesis ◽  
Atp Hydrolysis ◽  
Sirtuin 1 ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mild Heat ◽  
Beneficial Effects ◽  
Mitochondrial Dna Copy Number

During endurance exercise, most (≈75%) of the energy derived from the oxidation of metabolic fuels and ATP hydrolysis of muscle contraction is liberated as heat, the accumulation of which leads to an increase in body temperature. For example, the temperature of exercising muscles can rise to 40°C. Although severe heat injury can be deleterious, several beneficial effects of mild heat stress (HS), such as the improvement of insulin sensitivity in patients with type 2 diabetes, have been reported. However, among all cellular events induced by mild HS from physical activities, the direct effects and mechanisms of mild HS on mitochondrial biogenesis in skeletal muscle are least characterized. AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) are key energy-sensing molecules regulating mitochondrial biogenesis. In C2C12 myotubes, we found that 1 h mild HS at 40°C upregulated both AMPK activity and SIRT1 expression, as well as increased the expression of several mitochondrial biogenesis regulatory genes including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and transcription factors involved in mitochondrial biogenesis. In particular, PGC-1α expression was found to be transcriptionally regulated by mild HS. Additionally, after repeated mild HS for 5 days, protein levels of PGC-1α and several mitochondrial oxidative phosphorylation subunits were also upregulated. Repeated mild HS also significantly increased mitochondrial DNA copy number. In conclusion, these data show that mild HS is sufficient to induce mitochondrial biogenesis in C2C12 myotubes. Temperature-induced mitochondrial biogenesis correlates with activation of the AMPK-SIRT1-PGC-1α pathway. Therefore, it is possible that muscle heat production during exercise plays a role in mitochondrial biogenesis.

scholarly journals p53 is necessary for the adaptive changes in cellular milieu subsequent to an acute bout of endurance exercise

2014 ◽  
Vol 306 (3) ◽  
pp. C241-C249 ◽  
Author(s):  
Ayesha Saleem ◽  
Heather N. Carter ◽  
David A. Hood
Keyword(s):  
Endurance Exercise ◽  
Mitochondrial Biogenesis ◽  
Messenger Rna ◽  
Acute Exercise ◽  
Peroxisome Proliferator ◽  
Subsequent Increase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Acute Bout ◽  
Downstream Signaling ◽  
Exercise Induced

An acute bout of exercise activates downstream signaling cascades that ultimately result in mitochondrial biogenesis. In addition to inducing mitochondrial synthesis, exercise triggers the removal of damaged cellular material via autophagy and of dysfunctional mitochondria through mitophagy. Here, we investigated the necessity of p53 to the changes that transpire within the muscle upon an imposed metabolic and physiological challenge, such as a bout of endurance exercise. We randomly assigned wild-type (WT) and p53 knockout (KO) mice to control, acute exercise (AE; 90 min at 15 m/min), and AE + 3 h recovery (AER) groups and measured downstream alterations in markers of mitochondrial biogenesis, autophagy, and mitophagy. In the absence of p53, activation of p38 MAPK upon exercise was abolished, whereas CaMKII and AMP-activated protein kinase only displayed an attenuated enhancement in the AER group compared with WT mice. The translocation of peroxisome proliferator-activated receptor-γ coactivator-1 α to the nucleus was diminished and only observed in the AER group, and the subsequent increase in messenger RNA transcripts related to mitochondrial biogenesis with exercise and recovery was absent in the p53 KO animals. Whole-muscle autophagic and lysosomal markers did not respond to exercise, irrespective of the genotype of the exercised mice, with the exception of increased ubiquitination observed in KO mice with exercise. Markers of mitophagy were elevated in response to AE and AER conditions in both WT and p53 KO runners. The data suggest that p53 is important for the exercise-induced activation of mitochondrial synthesis and is integral in regulating autophagy during control conditions but not in response to exercise.

scholarly journals Endurance exercise is protective for mice with mitochondrial myopathy

2009 ◽  
Vol 106 (5) ◽  
pp. 1712-1719 ◽  
Author(s):  
Tina Wenz ◽  
Francisca Diaz ◽  
Dayami Hernandez ◽  
Carlos T. Moraes
Keyword(s):  
Mouse Model ◽  
Endurance Exercise ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Myopathy ◽  
Peroxisome Proliferator ◽  
Oxidase Deficiency ◽  
Peroxisome Proliferator Activated Receptor ◽  
Added Benefit ◽  
Exercise Induced ◽  
Generating System

Defects in the mitochondrial ATP-generating system are one of the most commonly inherited neurological disorders, but they remain without treatment. We have recently shown that modulation of the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) level in skeletal muscle of a mitochondrial myopathy mouse model offers a therapeutic approach. Here we analyzed if endurance exercise, which is known to be associated with an increased PGC-1α level in muscle, offers the same beneficial effect. We subjected male and female mice that develop a severe mitochondrial myopathy due to a cytochrome- c oxidase deficiency at 3 mo of age to endurance exercise training and monitored phenotypical and metabolic changes. Sedentary myopathy and wild-type mice were used as controls. Exercise increased PGC-1α in muscle, resulting in increased mitochondrial biogenesis, and successfully stimulated residual respiratory capacity in muscle tissue. As a consequence, ATP levels were increased in exercised mice compared with sedentary myopathy animals, which resulted in a delayed onset of the myopathy and a prolonged lifespan of the exercised mice. As an added benefit, endurance exercise induced antioxidant enzymes. The overall protective effect of endurance exercise delayed the onset of the mitochondrial myopathy and increased life expectancy in the mouse model. Thus stimulating residual oxidative phosphorylation function in the affected muscle by inducing mitochondrial biogenesis through endurance exercise might offer a valuable therapeutic intervention for mitochondrial myopathy patients.

scholarly journals Rhein Relieves Oxidative Stress in an Aβ1-42 Oligomer-Burdened Neuron Model by Activating the SIRT1/PGC-1α-Regulated Mitochondrial Biogenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhihui Yin ◽  
Xinyue Geng ◽  
Zhengyi Zhang ◽  
Ying Wang ◽  
Xiaoyan Gao
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Biogenesis ◽  
Antioxidant Defense System ◽  
Sirtuin 1 ◽  
Early Event ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Oxidative Stress ◽  
Nuclear Respiratory Factor ◽  
Nuclear Respiratory Factor 1

Neuronal mitochondrial oxidative stress induced by β-amyloid (Aβ) is an early event of Alzheimer’s disease (AD). Emerging evidence has shown that antioxidant therapy represents a promising therapeutic strategy for the treatment of AD. In this study, we investigated the antioxidant activity of rhein against Aβ1-42 oligomer-induced mitochondrial oxidative stress in primary neurons and proposed a potential antioxidant pathway involved. The results suggested that rhein significantly reduced reactive oxygen species (ROS) level, reversed the depletion of mitochondrial membrane potential, and protected neurons from oxidative stress-associated apoptosis. Moreover, further study indicated that rhein activated mitochondrial biogenesis accompanied by increased cytochrome C oxidase (CytOx) and superoxide dismutase (SOD) activities. CytOx on the respiratory chain inhibited the production of ROS from electron leakage and SOD helped to eliminate excess ROS. Finally, western blot analysis confirmed that rhein remarkedly increased the protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) together with its upstream deacetylase sirtuin 1 (SIRT1), and activated downstream transcription factor nuclear respiratory factor 1, promoting mitochondrial biogenesis. In conclusion, our results demonstrate that rhein activates mitochondrial biogenesis regulated by the SIRT1/PGC-1α pathway as an antioxidant defense system against Aβ1-42 oligomer-induced oxidative stress. These findings broaden our knowledge of improving mitochondrial biogenesis as an approach for relieving neuronal oxidative stress in AD.

scholarly journals A New Insight into an Alternative Therapeutic Approach to Restore Redox Homeostasis and Functional Mitochondria in Neurodegenerative Diseases

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 7
Author(s):  
Dong-Hoon Hyun ◽  
Jaewang Lee
Keyword(s):  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Redox Homeostasis ◽  
Protein Aggregates ◽  
Sirtuin 1 ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cellular Signalling

Neurodegenerative diseases are accompanied by oxidative stress and mitochondrial dysfunction, leading to a progressive loss of neuronal cells, formation of protein aggregates, and a decrease in cognitive or motor functions. Mitochondrial dysfunction occurs at the early stage of neurodegenerative diseases. Protein aggregates containing oxidatively damaged biomolecules and other misfolded proteins and neuroinflammation have been identified in animal models and patients with neurodegenerative diseases. A variety of neurodegenerative diseases commonly exhibits decreased activity of antioxidant enzymes, lower amounts of antioxidants, and altered cellular signalling. Although several molecules have been approved clinically, there is no known cure for neurodegenerative diseases, though some drugs are focused on improving mitochondrial function. Mitochondrial dysfunction is caused by oxidative damage and impaired cellular signalling, including that of peroxisome proliferator-activated receptor gamma coactivator 1α. Mitochondrial function can also be modulated by mitochondrial biogenesis and the mitochondrial fusion/fission cycle. Mitochondrial biogenesis is regulated mainly by sirtuin 1, NAD+, AMP-activated protein kinase, mammalian target of rapamycin, and peroxisome proliferator-activated receptor γ. Altered mitochondrial dynamics, such as increased fission proteins and decreased fusion products, are shown in neurodegenerative diseases. Due to the restrictions of a target-based approach, a phenotype-based approach has been performed to find novel proteins or pathways. Alternatively, plasma membrane redox enzymes improve mitochondrial function without the further production of reactive oxygen species. In addition, inducers of antioxidant response elements can be useful to induce a series of detoxifying enzymes. Thus, redox homeostasis and metabolic regulation can be important therapeutic targets for delaying the progression of neurodegenerative diseases.

scholarly journals Modified Si-Ni-San Decoction Ameliorates Central Fatigue by Improving Mitochondrial Biogenesis in the Rat Hippocampus

2018 ◽  
Vol 2018 ◽  
pp. 1-16
Author(s):  
Chenxia Han ◽  
Feng Li ◽  
Yan Liu ◽  
Jie Ma ◽  
Xue Yu ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Central Fatigue ◽  
Creatine Kinase Activity ◽  
Sirtuin 1 ◽  
Peroxisome Proliferator ◽  
Mitochondrial Ultrastructure ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Mitochondrial Dna Copy Number ◽  
Gene And Protein Expression

The traditional Chinese medicine (TCM) decoction Si-Ni-San (SNS) has been utilised for millennia to improve physiological coordination of the functions of the liver and spleen, which are regarded as the main pathological organs of central fatigue in TCM. This study evaluates the effect of a modified SNS (MSNS) formula on central fatigue in rats and explores molecular changes associated with hippocampal mitochondrial biogenesis. Central fatigue was induced through a 21-day sleep deprivation protocol. We assessed MSNS’s effects on behaviour, blood and liver biomarkers, and mitochondrial ultrastructure. We found that MSNS could reverse various signs of central fatigue such as its effects on hippocampal gene and protein expression levels of sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and nuclear respiratory factor 1 (NRF1). We also observed evidence of MSNS decreasing central fatigue, such as decreasing creatine kinase activity, decreasing levels of malondialdehyde and blood urea nitrogen, increasing lactate dehydrogenase and superoxide dismutase activities, increasing mitochondrial DNA copy number, and reversing mitochondrial ultrastructure changes. These findings suggest that MSNS can ameliorate central fatigue and that its molecular mechanism involves mitochondrial biogenesis enhancement mediated by hippocampal SIRT1, PGC-1α, and NRF1.

scholarly journals PPAR-gamma induced AKT3 expression increases levels of mitochondrial biogenesis driving prostate cancer

Oncogene ◽  
2021 ◽  
Vol 40 (13) ◽  
pp. 2355-2366
Author(s):  
Laura C. A. Galbraith ◽  
Ernest Mui ◽  
Colin Nixon ◽  
Ann Hedley ◽  
David Strachan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mitochondrial Biogenesis ◽  
Nuclear Export ◽  
Epithelial To Mesenchymal Transition ◽  
Ppar Gamma ◽  
Peroxisome Proliferator ◽  
Serine Threonine Kinase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mesenchymal Transition ◽  
And Function

AbstractPeroxisome Proliferator-Activated Receptor Gamma (PPARG) is one of the three members of the PPAR family of transcription factors. Besides its roles in adipocyte differentiation and lipid metabolism, we recently demonstrated an association between PPARG and metastasis in prostate cancer. In this study a functional effect of PPARG on AKT serine/threonine kinase 3 (AKT3), which ultimately results in a more aggressive disease phenotype was identified. AKT3 has previously been shown to regulate PPARG co-activator 1 alpha (PGC1α) localisation and function through its action on chromosome maintenance region 1 (CRM1). AKT3 promotes PGC1α localisation to the nucleus through its inhibitory effects on CRM1, a known nuclear export protein. Collectively our results demonstrate how PPARG over-expression drives an increase in AKT3 levels, which in turn has the downstream effect of increasing PGC1α localisation within the nucleus, driving mitochondrial biogenesis. Furthermore, this increase in mitochondrial mass provides higher energetic output in the form of elevated ATP levels which may fuel the progression of the tumour cell through epithelial to mesenchymal transition (EMT) and ultimately metastasis.

The Protective Mechanism of SIRT1 in the Regulation of Mitochondrial Biogenesis and Mitochondrial Autophagy in Alzheimer’s Disease

2021 ◽  
pp. 1-9
Author(s):  
Fan Ye ◽  
Anshi Wu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Biogenesis ◽  
Stress Responses ◽  
Histone Deacetylases ◽  
Neuronal Morphology ◽  
Protective Mechanism ◽  
Peroxisome Proliferator ◽  
Class Iii ◽  
Peroxisome Proliferator Activated Receptor

Silent information-regulated transcription factor 1 (SIRT1) is the most prominent and widely studied member of the sirtuins (a family of mammalian class III histone deacetylases). It is a nuclear protein, and the deacetylation of the peroxisome proliferator-activated receptor coactivator-1 has been extensively implicated in metabolic control and mitochondrial biogenesis and is the basis for studies into its involvement in caloric restriction and its effects on lifespan. The present study discusses the potentially protective mechanism of SIRT1 in the regulation of the mitochondrial biogenesis and autophagy involved in the modulation of Alzheimer’s disease, which may be correlated with the role of SIRT1 in affecting neuronal morphology, learning, and memory during development; regulating metabolism; counteracting stress responses; and maintaining genomic stability. Drugs that activate SIRT1 may offer a promising approach to treating Alzheimer’s disease

Sign in / Sign up

Export Citation Format

Share Document