scholarly journals Regulation of mitochondrial biogenesis

2010 ◽  
Vol 47 ◽  
pp. 69-84 ◽  
Author(s):  
François R. Jornayvaz ◽  
Gerald I. Shulman
Keyword(s):  
Mitochondrial Dysfunction ◽  
Mitochondrial Biogenesis ◽  
Molecular Mechanisms ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Mitochondrial Transcription Factor ◽  
Nuclear Respiratory Factor 1 ◽  
And Function ◽  
Amp Activated Protein Kinase

Although it is well established that physical activity increases mitochondrial content in muscle, the molecular mechanisms underlying this process have only recently been elucidated. Mitochondrial dysfunction is an important component of different diseases associated with aging, such as Type 2 diabetes and Alzheimer’s disease. PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α) is a co-transcriptional regulation factor that induces mitochondrial biogenesis by activating different transcription factors, including nuclear respiratory factor 1 and nuclear respiratory factor 2, which activate mitochondrial transcription factor A. The latter drives transcription and replication of mitochondrial DNA. PGC-1α itself is regulated by several different key factors involved in mitochondrial biogenesis, which will be reviewed in this chapter. Of those, AMPK (AMP-activated protein kinase) is of major importance. AMPK acts as an energy sensor of the cell and works as a key regulator of mitochondrial biogenesis. AMPK activity has been shown to decrease with age, which may contribute to decreased mitochondrial biogenesis and function with aging. Given the potentially important role of mitochondrial dysfunction in the pathogenesis of numerous diseases and in the process of aging, understanding the molecular mechanisms regulating mitochondrial biogenesis and function may provide potentially important novel therapeutic targets.

Beneficial Effect of Flavone Derivatives on Aβ-Induced Memory Deficit Is Mediated by Peroxisome Proliferator-Activated Receptor γ Coactivator 1α

2015 ◽  
Vol 34 (3) ◽  
pp. 274-283 ◽  
Author(s):  
Farshad Arsalandeh ◽  
Shahin Ahmadian ◽  
Forough Foolad ◽  
Fariba Khodagholi ◽  
Mahdi M. Farimani ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Neuroprotective Effect ◽  
Memory Function ◽  
Adenosine Monophosphate ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Mitochondrial Transcription Factor ◽  
Nuclear Respiratory Factor 1

In the present study, the neuroprotective effect of 5-hydroxy-6,7,4′-trimethoxyflavone (flavone 1), a natural flavone, was investigated in comparison with another flavone, 5,7,4′-trihydroxyflavone (flavone 2) on the hippocampus of amyloid beta (Aβ)-injected rats. Rats were treated with the 2 flavones (1 mg/kg/d) for 1 week before Aβ injection. Seven days after Aβ administration, memory function of rats was assessed in a passive avoidance test (PAT). Changes in the levels of mitochondrial transcription factor A (TFAM), peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α), phospho-adenosine monophosphate (AMP)-activated protein kinase (pAMPK), AMPK, phospho-cAMP-responsive element-binding protein (CREB), CREB, and nuclear respiratory factor 1 (NRF-1) proteins were determined by Western blot analysis. Our results showed an improvement in memory in rats pretreated with flavonoids. At the molecular level, phosphorylation of CREB, known as the master modulator of memory processes, increased. On the other hand, the level of mitochondrial biogenesis factors, PGC-1α and its downstream molecules NRF-1 and TFAM significantly increased by dietary administration of 2 flavones. In addition, flavone 1 and flavone 2 prevented mitochondrial swelling and mitochondrial membrane potential reduction. Our results provided evidence that flavone 1 is more effective than flavone 2 presumably due to its O-methylated groups. In conclusion, it seems that in addition to classical antioxidant effect, flavones exert part of their protective effects through mitochondrial biogenesis.

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 SIRT1 Activation by Resveratrol Alleviates Cardiac Dysfunction via Mitochondrial Regulation in Diabetic Cardiomyopathy Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Sai Ma ◽  
Jing Feng ◽  
Ran Zhang ◽  
Jiangwei Chen ◽  
Dong Han ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Dynamics ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Beneficial Effects ◽  
Mitochondrial Regulation ◽  
And Function

Background. Diabetic cardiomyopathy (DCM) is a major threat for diabetic patients. Silent information regulator 1 (SIRT1) has a regulatory effect on mitochondrial dynamics, which is associated with DCM pathological changes. Our study aims to investigate whether resveratrol, a SRIT1 activator, could exert a protective effect against DCM. Methods and Results. Cardiac-specific SIRT1 knockout (SIRT1KO) mice were generated using Cre-loxP system. SIRT1KO mice displayed symptoms of DCM, including cardiac hypertrophy and dysfunction, insulin resistance, and abnormal glucose metabolism. DCM and SIRT1KO hearts showed impaired mitochondrial biogenesis and function, while SIRT1 activation by resveratrol reversed this in DCM mice. High glucose caused increased apoptosis, impaired mitochondrial biogenesis, and function in cardiomyocytes, which was alleviated by resveratrol. SIRT1 deletion by both SIRT1KO and shRNA abolished the beneficial effects of resveratrol. Furthermore, the function of SIRT1 is mediated via the deacetylation effect on peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), thus inducing increased expression of nuclear respiratory factor 1 (NRF-1), NRF-2, estrogen-related receptor-α (ERR-α), and mitochondrial transcription factor A (TFAM). Conclusions. Cardiac deletion of SIRT1 caused phenotypes resembling DCM. Activation of SIRT1 by resveratrol ameliorated cardiac injuries in DCM through PGC-1α-mediated mitochondrial regulation. Collectively, SIRT1 may serve as a potential therapeutic target for DCM.

Activation of SIRT1 Alleviates Mitochondrial Dysfunction in The Trigeminal Nucleus Caudalis in a Rat Model of Chronic Migraine

2020 ◽  
Author(s):  
jie liang ◽  
xue zhou ◽  
jiang wang ◽  
zhaoyang fei ◽  
guangcheng qin ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Chronic Migraine ◽  
Rat Model ◽  
Vital Role ◽  
Peroxisome Proliferator ◽  
Trigeminal Nucleus ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Trigeminal Nucleus Caudalis ◽  
Nuclear Respiratory Factor 1

Abstract Background: The mechanism of chronic migraine (CM) is still unclear and mitochondrial dysfunction plays a possible role in migraine pathophysiology. Silent information regulator 1 (SIRT1) plays a vital role in mitochondrial dysfunction in many diseases, but there is no information about SIRT1 in CM.The aim of this study was to explore the role of SIRT1 in mitochondrial dysfunction in CM. Methods： A rat model was established through repeated dural infusions of inflammatory soup (IS) for seven days to simulate CM attacks. Cutaneous hyperalgesia caused by the repeated infusions of IS was detected using the von Frey test. Then, we detected SIRT1 expression in the trigeminal nucleus caudalis (TNC). To explore the effect of SIRT1 on mitochondrial dysfunction in CM rats, we examined whether SRT1720, an activator of SIRT1, altered mitochondrial dysfunction in CM rats. Results： Repeated infusions of IS resulted in cutaneous hyperalgesia accompanied bydownregulation of SIRT1.SRT1720 significantly alleviated the cutaneous hyperalgesia induced by repeated infusions of IS. Furthermore, activation of SIRT1 markedly increased the expression of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha(PGC-1α), transcription factor A (TFAM), nuclear respiratory factor 1 (NRF-1), and nuclear respiratory factor 2(NRF-2) mitochondrial DNA (mtDNA) and increased the ATP content and mitochondrial membrane potential. Conclusions ：Our results indicate that SIRT1 may have an effect on mitochondrial dysfunction in CM rats. Activation of SIRT1 has a protective effect on mitochondrial function in CM rats.

scholarly journals Telomeric injury by KML001 in human T cells induces mitochondrial dysfunction through the p53-PGC-1α pathway

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Madison Schank ◽  
Juan Zhao ◽  
Ling Wang ◽  
Zhengke Li ◽  
Dechao Cao ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mitochondrial Dysfunction ◽  
Cell Aging ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Nuclear Respiratory Factor 1 ◽  
Human T Cell ◽  
Wide Range

AbstractTelomere erosion and mitochondrial dysfunction are prominent features of aging cells with progressive declines of cellular functions. Whether telomere injury induces mitochondrial dysfunction in human T lymphocytes, the major component of adaptive host immunity against infection and malignancy, remains unclear. We have recently shown that disruption of telomere integrity by KML001, a telomere-targeting drug, induces T cell senescence and apoptosis via the telomeric DNA damage response (DDR). In this study, we used KML001 to further investigate the role and mechanism of telomere injury in mitochondrial dysregulation in aging T cells. We demonstrate that targeting telomeres by KML001 induces mitochondrial dysfunction, as evidenced by increased mitochondrial swelling and decreased mitochondrial membrane potential, oxidative phosphorylation, mitochondrial DNA content, mitochondrial respiration, oxygen consumption, glycolysis, and ATP energy production. Mechanistically, we found that the KML001-induced telomeric DDR activated p53 signaling, which in turn repressed the expression of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) and nuclear respiratory factor 1 (NRF-1), leading to T cell mitochondrial dysfunction. These results, forging a direct link between telomeric and mitochondrial biology, shed new light on the human T cell aging network, and demonstrate that the p53-PGC-1α-NRF-1 axis contributes to mitochondrial dysfunction in the setting of telomeric DDR. This study suggests that targeting this axis may offer an alternative, novel approach to prevent telomere damage-mediated mitochondrial and T cell dysfunctions to combat a wide range of immune aging-associated human diseases.

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 Dietary Sea Buckthorn Pomace Induces Beige Adipocyte Formation in Inguinal White Adipose Tissue in Lambs

Animals ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 193 ◽  
Author(s):  
Ting Zhang ◽  
Buhao Deng ◽  
Ruixin Zhang ◽  
Xuze Qin ◽  
Jianxin Zhang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Glucose Transporter ◽  
Sea Buckthorn ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beige Adipocyte ◽  
Nuclear Respiratory Factor ◽  
Mitochondrial Transcription Factor ◽  
Nuclear Respiratory Factor 1

The sea buckthorn contains substantial amounts of bioactive compounds. The objective of this study was to investigate the effects of dietary sea buckthorn pomace (SBP) on sheep beige adipocyte formation. A total of thirty lambs were equally divided into three groups and fed with diets containing different levels of SBP: 0% SBP (Control), 7.8% SBP (7.8SBP), and 16.0% SBP (16SBP). The results showed that dietary SBP affected inguinal adipocytes’ size distribution, and increased both UCP1 protein content (p < 0.05) and mitochondrial numbers (p < 0.05). mRNA expression of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A were increased when animals were subjected to 16% SBP (p < 0.05). Supplementation with 16% SBP increased CCAAT/enhancer-binding protein β content (p < 0.05) and PR domain containing 16 mRNA abundance (p < 0.05). Consistently, inguinal white adipose tissue (iWAT) from the 16SBP group exhibited increased insulin sensitivity, which was associated with elevated glucose transporter 4 abundance (p < 0.05). Importantly, AMP-activated protein kinase (AMPK) was activated in the 16SBP group (p < 0.05). Collectively, these results suggest that dietary SBP promotes iWAT browning in lambs, which might be through the activation of the AMPK–PGC-1α–UCP1 signaling pathway.

scholarly journals Cyclovirobuxine D Attenuates Doxorubicin-Induced Cardiomyopathy by Suppression of Oxidative Damage and Mitochondrial Biogenesis Impairment

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Qian Guo ◽  
Jiabin Guo ◽  
Rong Yang ◽  
Hui Peng ◽  
Jun Zhao ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Mitochondrial Biogenesis ◽  
Peroxisome Proliferator ◽  
Cytochrome C Release ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Nuclear Respiratory Factor 1 ◽  
Mitochondrial Dna Copy Number ◽  
Cardiac Contractile Dysfunction ◽  
Induced Apoptosis

The clinical application of doxorubicin (DOX) is compromised by its cardiac toxic effect. Cyclovirobuxine D (CVB-D) is a steroid alkaloid extracted from a traditional Chinese medicine,Buxus microphylla. Our results showed that CVB-D pretreatment markedly attenuated DOX-induced cardiac contractile dysfunction and histological alterations. By using TUNEL assay and western blot analysis, we found that CVB-D pretreatment reduced DOX-induced apoptosis of myocardial cells and mitochondrial cytochrome c release to cytosol. CVB-D pretreatment ameliorated DOX-induced cardiac oxidative damage including lipid peroxidation and protein carbonylation and a decrease in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG). Moreover, CVB-D was found to prevent DOX-induced mitochondrial biogenesis impairment as evidenced by preservation of peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α) and nuclear respiratory factor 1 (NRF1), as well as mitochondrial DNA copy number. These findings demonstrate that CVB-D protects against DOX-induced cardiomyopathy, at least in part, by suppression of oxidative damage and mitochondrial biogenesis impairment.

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.

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