scholarly journals The role of mitochondria in physical activity and its adaptation on aging

2015 ◽  
Vol 32 (04) ◽  
pp. 257-263
Author(s):  
M. Ferro ◽  
G. Rodrigues ◽  
R. De Souza
Keyword(s):  
Physical Activity ◽  
Muscle Tissue ◽  
Mitochondrial Biogenesis ◽  
Oxidative Capacity ◽  
Mitochondrial Activity ◽  
Nutritional Interventions ◽  
Nuclear Respiratory Factor ◽  
Nuclear Respiratory Factor 1 ◽  
Body Tissues ◽  
Mitochondrial Functions

Abstract Introduction: The mitochondria are essential in numerous physiological processes, including energy production, redox potential, modulation of calcium and several metabolic pathways. When the number or mitochondrial activity is insufficient, the human body quickly goes into fatigue due to ATP deficiency. Methods: The principal data base were used: PubMed, Medline, Scielo and Lilacs. Keywords used were: mitochondrial biogenesis, aging, organic acids, enzyme changes and respiratory chain. Groups considered: young and aged. Types of training: aerobic and anaerobic. Papers dealing with pathogies were not considered. The oxidative capacity of muscle tissue and the preservation of mitochondria depends on the mitochondrial biogenesis that occurs through the transcription factor proliferator-activator receptor-γ coactivatorlα (PGC-1α). The oxidative process and the progressive change in the biogenesis of mitochondria have direct influence on the aging of muscle tissue. The regulation of the biogenesis occurs through the PGC-1α combined with nuclear respiratory factor 1 (NRF1). Abnormalities in mitochondria and mutagenesis in mitochondrial DNA (mtDNA) are tied to multi-system degeneration, as well as intolerance to stress, and decreased energy in aging in humans, rats and monkeys. The mitochondrial functions are dramatically altered in heart disease, demonstrating a decrease in expression of PGC-1α, which plays a key role in the coordination of energy metabolism. This process can be reversed by the PGC-1α itself. The identification of compounds capable of activating the transcription of PGC-1α could be part of future therapies to reverse pathologies associated with the decline of this organelle. Morpho-physiological and biochemical changes of these organelles directly reflect the physiological performance of all body tissues. Conclusion: evidence demonstrated that physical activity, both in young and aged is a major ally in mitochondrial biogenesis by activating the transcription of PGC - 1α and that future nutritional interventions may be of great aid in the health and performance of mitochondria. However, further studies are needed in order to understand and clarify this operation, since currently these mechanisms are only partially known.

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.

Abstract 86: Cardiomyocyte-Specific Ablation of Nuclear Respiratory Factor 1 in the Mouse Leads to Dysregulation of Mitochondrial Biogenesis, Apoptosis, and Heart Failure

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Jeffrey E Keenan ◽  
Hagir Sulliman ◽  
Allison Ulrich ◽  
Lan Mao ◽  
Claude A Piantadosi
Keyword(s):  
Heart Failure ◽  
Mitochondrial Biogenesis ◽  
Structural Integrity ◽  
Left Ventricular ◽  
Nuclear Condensation ◽  
Nuclear Respiratory Factor ◽  
Protein Levels ◽  
Mitochondrial Homeostasis ◽  
Nuclear Respiratory Factor 1

The DNA-binding transcription factor Nuclear Respiratory Factor 1 (NRF1) regulates mitochondrial homeostasis. Its constitutive ablation in the mouse is embryonically lethal (~E3.5). This has limited our understanding of NRF1 functionality in the heart, where mitochondrial dysfunction is often a major pathogenic factor. Therefore, we generated conditional cardiomyocyte-specific NRF1 knockout mice (MYH6-mer-Cre-mer-NRF1fl/fl or NRFfl/fl) to elucidate the role of cardiac NRF1. Two weeks after NRF1 silencing, echocardiography of NRF1fl/fl hearts revealed significant reductions in left ventricular fractional shortening (Figure A). Histology demonstrated degradation of cellular structural integrity and nuclear condensation (Figure B), with a high number of TUNEL positive nuclei compared to littermate controls (MYH6-mer-Cre-mer-NRF-1wt), indicative of apoptosis (37.8% vs. 1.1%, p < 0.001). The mRNA and protein levels of key mediators of mitochondrial biogenesis were evaluated by real-time RT-PCR and immunoblotting (Figure C & D). Compared to littermate controls, there was down-regulation of the mitochondrial encoded NADH dehydrogenase 1, implying a reduction of functional mitochondrial mass. Key biogenesis regulators PGC1-α (protein only), Nfe2l2, and NRF2 were also reduced. In total, these data support that dysregulation of mitochondrial biogenesis after loss of NRF1 results in cardiomyocyte apoptosis and reduced left ventricular function. These findings and further delineation of the mechanisms involved should lay the foundation for the exploitation of NRF1 as a therapeutic target in heart failure.

scholarly journals Lipopolysaccharide Stimulates Mitochondrial Biogenesis via Activation of Nuclear Respiratory Factor-1

2003 ◽  
Vol 278 (42) ◽  
pp. 41510-41518 ◽  
Author(s):  
Hagir B. Suliman ◽  
Martha S. Carraway ◽  
Karen E. Welty-Wolf ◽  
A. Richard Whorton ◽  
Claude A. Piantadosi
Keyword(s):  
Mitochondrial Biogenesis ◽  
Nuclear Respiratory Factor ◽  
Nuclear Respiratory Factor 1

scholarly journals A new live-cell reporter strategy to simultaneously monitor mitochondrial biogenesis and morphology

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Linn Iren Hodneland Nilsson ◽  
Ina Katrine Nitschke Pettersen ◽  
Julie Nikolaisen ◽  
David Micklem ◽  
Hege Avsnes Dale ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Fluorescent Protein ◽  
Live Cell ◽  
Mitochondrial Morphology ◽  
Reporter Construct ◽  
Nuclear Respiratory Factor ◽  
Nuclear Respiratory Factor 1 ◽  
Vital Functions ◽  
Dependent Protein ◽  
Green Fluorescent

Abstract Changes in mitochondrial amount and shape are intimately linked to maintenance of cell homeostasis via adaptation of vital functions. Here, we developed a new live-cell reporter strategy to simultaneously monitor mitochondrial biogenesis and morphology. This was achieved by making a genetic reporter construct where a master regulator of mitochondrial biogenesis, nuclear respiratory factor 1 (NRF-1), controls expression of mitochondria targeted green fluorescent protein (mitoGFP). HeLa cells with the reporter construct demonstrated inducible expression of mitoGFP upon activation of AMP-dependent protein kinase (AMPK) with AICAR. We established stable reporter cells where the mitoGFP reporter activity corresponded with mitochondrial biogenesis both in magnitude and kinetics, as confirmed by biochemical markers and confocal microscopy. Quantitative 3D image analysis confirmed accordant increase in mitochondrial biomass, in addition to filament/network promoting and protecting effects on mitochondrial morphology, after treatment with AICAR. The level of mitoGFP reversed upon removal of AICAR, in parallel with decrease in mtDNA. In summary, we here present a new GFP-based genetic reporter strategy to study mitochondrial regulation and dynamics in living cells. This combinatorial reporter concept can readily be transferred to other cell models and contexts to address specific physiological mechanisms.

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 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.

scholarly journals The Use of Antioxidants as Potential Co-Adjuvants to Treat Chronic Chagas Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1022
Author(s):  
Edio Maldonado ◽  
Diego A. Rojas ◽  
Fabiola Urbina ◽  
Aldo Solari
Keyword(s):  
Gene Expression ◽  
Adjuvant Therapy ◽  
Chagas Disease ◽  
Latin American ◽  
Mitochondrial Biogenesis ◽  
Antioxidant Defenses ◽  
Myocardial Inflammation ◽  
Nuclear Respiratory Factor ◽  
Mitochondrial Functions ◽  
Activate Gene

Chagas disease is a neglected tropical disease caused by the flagellated protozoa Trypanosome cruzi. This illness affects to almost 8–12 million people worldwide, however, is endemic to Latin American countries. It is mainly vectorially transmitted by insects of the Triatominae family, although other transmission routes also exist. T. cruzi-infected cardiomyocytes at the chronic stage of the disease display severe mitochondrial dysfunction and high ROS production, leading to chronic myocardial inflammation and heart failure. Under cellular stress, cells usually can launch mitochondrial biogenesis in order to restore energy loss. Key players to begin mitochondrial biogenesis are the PGC-1 (PPARγ coactivator 1) family of transcriptional coactivators, which are activated in response to several stimuli, either by deacetylation or dephosphorylation, and in turn can serve as coactivators for the NRF (nuclear respiratory factor) family of transcription factors. The NRF family of transcriptional activators, namely NRF1 and NRF2, can activate gene expression of oxidative phosphorylation (OXPHOS) components, mitochondrial transcriptional factor (Tfam) and nuclear encoded mitochondrial proteins, leading to mitochondrial biogenesis. On the other hand, NRF2 can activate gene expression of antioxidant enzymes in response to antioxidants, oxidants, electrophile compounds, pharmaceutical and dietary compounds in a mechanism dependent on KEAP1 (Kelch-like ECH-associated protein 1). Since a definitive cure to treat Chagas disease has not been found yet; the use of antioxidants a co-adjuvant therapy has been proposed in an effort to improve mitochondrial functions, biogenesis, and the antioxidant defenses response. Those antioxidants could activate different pathways to begin mitochondrial biogenesis and/or cytoprotective antioxidant defenses. In this review we discuss the main mechanisms of mitochondrial biogenesis and the NRF2-KEAP1 activation pathway. We also reviewed the antioxidants used as co-adjuvant therapy to treat experimental Chagas disease and their action mechanisms and finish with the discussion of antioxidant therapy used in Chagas disease patients.

scholarly journals The Differential Expression of Mitochondrial Function-Associated Proteins and Antioxidant Enzymes during Bovine Herpesvirus 1 Infection: A Potential Mechanism for Virus Infection-Induced Oxidative Mitochondrial Dysfunction

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaotian Fu ◽  
Xinyi Jiang ◽  
Xinye Chen ◽  
Liqian Zhu ◽  
Gaiping Zhang
Keyword(s):  
Antioxidant Enzymes ◽  
Virus Infection ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Respiratory Chain ◽  
Productive Infection ◽  
Nuclear Respiratory Factor ◽  
Nuclear Respiratory Factor 1 ◽  
Associated Proteins ◽  
Critical Components

Reactive oxidative species (ROS) are important inflammatory mediators. Electrons escaping from the mitochondrial electron transport chain (ETC) during oxidative phosphorylation (OXPHOS) in the mitochondrial respiratory chain (RC) complexes contribute to ROS production. The cellular antioxidant enzymes are important for maintaining ROS release at the physiological levels. It has been reported that BoHV-1 infection induces overproduction of ROS and oxidative mitochondrial dysfunction in cell cultures. In this study, we found that chemical interruption of RC complexes by TTFA (an inhibitor of RC complex II), NaN3 (an inhibitor of RC complex IV), and oligomycin A (an inhibitor of ATP synthase) consistently decreased virus productive infection, suggesting that the integral processes of RC complexes are important for the virus replication. The virus infection significantly increased the expression of subunit SDHB (succinate dehydrogenase) and MTCO1 (cytochrome c oxidase subunit I), critical components of RC complexes II and IV, respectively. The expression of antioxidant enzymes including superoxide dismutase 1 (SOD1), SOD2, catalase (CAT), and glutathione peroxidase 4 (GPX4) was differentially affected following the virus infection. The protein TFAM (transcription factor A, mitochondrial) stimulated by either nuclear respiratory factor 1 (NRF1) or NRF2 is a key regulator of mitochondrial biogenesis. Interestingly, the virus infection at the late stage (at 16 h after infection) stimulated TFAM expression but decreased the levels of both NRF1 and NRF2, indicating that virus infection activated TFAM signaling independent of either NRF1 or NRF2. Overall, this study provided evidence that BoHV-1 infection altered the expression of molecules associated with RC complexes, antioxidant enzymes, and mitochondrial biogenesis-related signaling NRF1/NRF2/TFAM, which correlated with the previous report that virus infection induces ROS overproduction and mitochondrial dysfunction.

Sign in / Sign up

Export Citation Format

Share Document