Pyruvate induces mitochondrial biogenesis by a PGC-1 α-independent mechanism

2007 ◽  
Vol 292 (5) ◽  
pp. C1599-C1605 ◽  
Author(s):  
Leanne Wilson ◽  
Qing Yang ◽  
Joseph D. Szustakowski ◽  
P. Scott Gullicksen ◽  
Reza Halse
Keyword(s):  
Mitochondrial Biogenesis ◽  
Energy Demand ◽  
Mitochondrial Protein ◽  
Oxidative Capacity ◽  
Sodium Pyruvate ◽  
Mitochondrial Mass ◽  
Primary Myoblasts ◽  
Independent Mechanism ◽  
Energy Sensing ◽  
The Impact

Oxidative cells increase mitochondrial mass in response to stimuli such as changes in energy demand or cellular differentiation. This plasticity enables the cell to adapt dynamically to achieve the necessary oxidative capacity. However, the pathways involved in triggering mitochondrial biogenesis are poorly defined. The present study examines the impact of altering energy provision on mitochondrial biogenesis in muscle cells. C2C12 myoblasts were chronically treated with supraphysiological levels of sodium pyruvate for 72 h. Treated cells exhibited increased mitochondrial protein expression, basal respiratory rate, and maximal oxidative capacity. The increase in mitochondrial biogenesis was independent of increases in peroxisomal proliferator activator receptor-γ coactivator-1α (PGC-1α) and PGC-1β mRNA expression. To further assess whether PGC-1α expression was necessary for pyruvate action, cells were infected with adenovirus containing shRNA for PGC-1α before treatment with pyruvate. Despite a 70% reduction in PGC-1α mRNA, the effect of pyruvate was preserved. Furthermore, pyruvate induced mitochondrial biogenesis in primary myoblasts from PGC-1α null mice. These data suggest that regulation of mitochondrial biogenesis by pyruvate in myoblasts is independent of PGC-1α, suggesting the existence of a novel energy-sensing pathway regulating oxidative capacity.

scholarly journals An Autosomal Dominant Form of Ras-Related C3 Botulinum Toxin Substrate 2 (RAC2) Is Associated with Haematopoiesis Failure

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4306-4306
Author(s):  
Chantal Lagresle-Peyrou ◽  
Aurélien Olichon ◽  
Hanem Sadek ◽  
Philippe Roche ◽  
Claudine Tardy ◽  
...  
Keyword(s):  
Energy Demand ◽  
Clinical Phenotype ◽  
Severe Combined Immunodeficiency ◽  
Mitochondrial Protein ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Mitochondrial Activity ◽  
Hematopoietic Stem ◽  
Screening Programs ◽  
The Impact

Abstract Severe combined immunodeficiencies (SCIDs) constitute a heterogeneous group of life-threatening genetic disorders that typically present in the first year of life. Reticular dysgenesis (RD) is an autosomal recessive form of human Severe Combined Immunodeficiency (SCIDs) characterized by the absence of blood neutrophils and T lymphocytes. This pathology is due to biallelic mutations in the adenylate kinase 2 (AK2) gene, encoding for a mitochondrial protein which regulates the homeostasis of adenine nucleotides. In three newborns presenting a RD-like clinical phenotype as frequent infections and a profound leukopenia, we identified an heterozygous dominant missense mutation in the gene coding for Rac Family Small GTPase 2 (RAC2) protein (p.G12R). Hematopoietic stem cell transplantation (HSCT) performed soon after birth was successful in two out of the three patients attesting that the inherited defect was intrinsic and not micro-environmental. RAC2 protein belongs to the Rac subfamily of RHO small GTPases. In the inactive GDP-bound state, RAC2 is located in the cytosol and upon stimulation, the active RAC2-GTP-bound form translocates to the plasma membrane. Unlike the other members of the Rac subfamily (RAC1 and RAC3), RAC2 is mostly expressed on hematopoietic cells and during T cell differentiation. To gain insight into the disease, we transduced human hematopoietic stem and progenitor cells (HSPCs) with a lentiviral construct containing the RAC2 mutated form. The mutation inhibits HSPCs proliferation and differentiation toward the myeloid and lymphoid lineages reproducing the patients' clinical phenotype. In this condition, we also observed high apoptosis level and an alteration of mitochondrial activity and Ros production. In a biochemical model, we demonstrated that the substitution of the glycine (G) amino-acid by a bulky flexible arginine (R) may prevent GTP hydrolysis. Lastly, our findings suggest that RAC2 gene sequencing must be considered in newborn screening programs for SCID detection. To decipher the mechanisms regulating RAC2 functions, we studied the impact of the p.G12R mutation on a human AML cell line expressing RAC2 protein. Our preliminary data highlight that the cell cycle and mitochondrial activity are disrupted by G12R mutation. By holotomography, we also observed morphological changes and accumulation of lipid droplets into the cells. All these data suggest that RAC2 defective signalling pathway is linked to cell metabolism imbalance and further investigations are ongoing to better understand how RAC2 controls cell energy demand, especially during differentiation. Disclosures Cavazzana: Smart Immune: Other: co-founder.

Control of mitochondrial biogenesis, ROS level, and cytosolic Ca2+ concentration during the cell cycle and the onset of differentiation in L6E9 myoblasts

2009 ◽  
Vol 296 (5) ◽  
pp. C1185-C1194 ◽  
Author(s):  
Vanessa E. Jahnke ◽  
Odile Sabido ◽  
Damien Freyssenet
Keyword(s):  
Cell Cycle ◽  
Mitochondrial Biogenesis ◽  
Energy Demand ◽  
Mitochondrial Protein ◽  
Nuclear Gene ◽  
Muscle Cells ◽  
S Phase ◽  
Retrograde Signaling ◽  
Peroxisome Proliferator ◽  
Activated T Cells

Mitochondria can sense signals linked to changes in energy demand to affect nuclear gene expression. This retrograde signaling pathway is presumed to be involved in the regulation of myoblast proliferation and differentiation. We have investigated the regulation of mitochondrial biogenesis and production of putative retrograde signaling agents [hydrogen peroxide (H2O2) and Ca2+] during the cell cycle and the onset of differentiation in L6E9 muscle cells. The biosynthesis of cardiolipin and mitochondrial proteins was mainly achieved in S phase, whereas the expression of mitochondrial biogenesis factors [peroxisome proliferator-activated receptor (PPAR)-α, PPAR-δ, and neuronal nitric oxide synthase 1] was regularly increased from G1 to G2M phase. In agreement with the increase in mitochondrial membrane potential, mitochondria in S and G2M phases have a significantly higher H2O2 level when compared with G1 phase. By contrast, the onset of differentiation was characterized by a marked reduction in mitochondrial protein expression and mitochondrial H2O2 level. The capacity of mitochondria to release Ca2+ in response to a metabolic challenge was significantly decreased at the onset of differentiation. Finally, an increase in calmodulin expression in S and G2M phases and a transitory increase in phosphorylated nuclear factor of activated T cells (NFAT) c3 in S phase was observed. NFATc3 phosphorylation was markedly decreased at the onset of differentiation. Our data point to functional links between the control of mitochondrial biogenesis and the regulation of the level of retrograde signaling agents during the cell cycle and the onset of differentiation in L6E9 muscle cells.

Mild mitochondrial uncoupling does not affect mitochondrial biogenesis but downregulates pyruvate carboxylase in adipocytes: role for triglyceride content reduction

2012 ◽  
Vol 302 (9) ◽  
pp. E1123-E1141 ◽  
Author(s):  
Aurélia De Pauw ◽  
Stéphane Demine ◽  
Silvia Tejerina ◽  
Marc Dieu ◽  
Edouard Delaive ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Pyruvate Carboxylase ◽  
Mitochondrial Protein ◽  
Functional Study ◽  
Mitochondrial Uncoupling ◽  
Triglyceride Accumulation ◽  
Qualitative Approaches ◽  
Mitochondrial Dna Copy Number ◽  
Triglyceride Content ◽  
The Impact

In adipocytes, mitochondrial uncoupling is known to trigger a triglyceride loss comparable with the one induced by TNFα, a proinflammatory cytokine. However, the impact of a mitochondrial uncoupling on the abundance/composition of mitochondria and its connection with triglyceride content in adipocytes is largely unknown. In this work, the effects of a mild mitochondrial uncoupling triggered by FCCP were investigated on the mitochondrial population of 3T3-L1 adipocytes by both quantitative and qualitative approaches. We found that mild mitochondrial uncoupling does not stimulate mitochondrial biogenesis in adipocytes but induces an adaptive cell response characterized by quantitative modifications of mitochondrial protein content. Superoxide anion radical level was increased in mitochondria of both TNFα- and FCCP-treated adipocytes, whereas mitochondrial DNA copy number was significantly higher only in TNFα-treated cells. Subproteomic analysis revealed that the abundance of pyruvate carboxylase was reduced significantly in mitochondria of TNFα- and FCCP-treated adipocytes. Functional study showed that overexpression of this major enzyme of lipid metabolism is able to prevent the triglyceride content reduction in adipocytes exposed to mitochondrial uncoupling or TNFα. These results suggest a new mechanism by which the effects of mitochondrial uncoupling might limit triglyceride accumulation in adipocytes.

scholarly journals Case study of a water bioengineering construction site in Austria. Ecological aspects and application of an environmental life cycle assessment model

2021 ◽  
Author(s):  
M. von der Thannen ◽  
S. Hoerbinger ◽  
C. Muellebner ◽  
H. Biber ◽  
H. P. Rauch
Keyword(s):  
Global Warming ◽  
Life Cycle Assessment ◽  
Life Cycle ◽  
Energy Demand ◽  
Assessment Model ◽  
Construction Site ◽  
Negative Effects ◽  
Environmental Life Cycle Assessment ◽  
The Impact ◽  
Soil And Water

AbstractRecently, applications of soil and water bioengineering constructions using living plants and supplementary materials have become increasingly popular. Besides technical effects, soil and water bioengineering has the advantage of additionally taking into consideration ecological values and the values of landscape aesthetics. When implementing soil and water bioengineering structures, suitable plants must be selected, and the structures must be given a dimension taking into account potential impact loads. A consideration of energy flows and the potential negative impact of construction in terms of energy and greenhouse gas balance has been neglected until now. The current study closes this gap of knowledge by introducing a method for detecting the possible negative effects of installing soil and water bioengineering measures. For this purpose, an environmental life cycle assessment model has been applied. The impact categories global warming potential and cumulative energy demand are used in this paper to describe the type of impacts which a bioengineering construction site causes. Additionally, the water bioengineering measure is contrasted with a conventional civil engineering structure. The results determine that the bioengineering alternative performs slightly better, in terms of energy demand and global warming potential, than the conventional measure. The most relevant factor is shown to be the impact of the running machines at the water bioengineering construction site. Finally, an integral ecological assessment model for applications of soil and water bioengineering structures should point out the potential negative effects caused during installation and, furthermore, integrate the assessment of potential positive effects due to the development of living plants in the use stage of the structures.

scholarly journals Impact of Passive Energy Efficiency Measures on Cooling Energy Demand in an Architectural Campus Building in Karachi, Pakistan

2021 ◽  
Vol 13 (13) ◽  
pp. 7251
Author(s):  
Mushk Bughio ◽  
Muhammad Shoaib Khan ◽  
Waqas Ahmed Mahar ◽  
Thorsten Schuetze
Keyword(s):  
Energy Efficiency ◽  
Energy Demand ◽  
Electricity Consumption ◽  
Information Modeling ◽  
Base Case ◽  
Energy Efficiency Measures ◽  
Efficiency Measures ◽  
The Impact ◽  
Cooling Energy Demand ◽  
Campus Building

Electric appliances for cooling and lighting are responsible for most of the increase in electricity consumption in Karachi, Pakistan. This study aims to investigate the impact of passive energy efficiency measures (PEEMs) on the potential reduction of indoor temperature and cooling energy demand of an architectural campus building (ACB) in Karachi, Pakistan. PEEMs focus on the building envelope’s design and construction, which is a key factor of influence on a building’s cooling energy demand. The existing architectural campus building was modeled using the building information modeling (BIM) software Autodesk Revit. Data related to the electricity consumption for cooling, building masses, occupancy conditions, utility bills, energy use intensity, as well as space types, were collected and analyzed to develop a virtual ACB model. The utility bill data were used to calibrate the DesignBuilder and EnergyPlus base case models of the existing ACB. The cooling energy demand was compared with different alternative building envelope compositions applied as PEEMs in the renovation of the existing exemplary ACB. Finally, cooling energy demand reduction potentials and the related potential electricity demand savings were determined. The quantification of the cooling energy demand facilitates the definition of the building’s electricity consumption benchmarks for cooling with specific technologies.

scholarly journals Advances of 2nd Life Applications for Lithium Ion Batteries from Electric Vehicles Based on Energy Demand

2021 ◽  
Vol 13 (10) ◽  
pp. 5726
Author(s):  
Aleksandra Wewer ◽  
Pinar Bilge ◽  
Franz Dietrich
Keyword(s):  
Life Cycle ◽  
Lithium Ion Batteries ◽  
Electric Vehicles ◽  
Energy Demand ◽  
Lithium Ion ◽  
Life Cycles ◽  
Future Research ◽  
Research Areas ◽  
Study Results ◽  
The Impact

Electromobility is a new approach to the reduction of CO2 emissions and the deceleration of global warming. Its environmental impacts are often compared to traditional mobility solutions based on gasoline or diesel engines. The comparison pertains mostly to the single life cycle of a battery. The impact of multiple life cycles remains an important, and yet unanswered, question. The aim of this paper is to demonstrate advances of 2nd life applications for lithium ion batteries from electric vehicles based on their energy demand. Therefore, it highlights the limitations of a conventional life cycle analysis (LCA) and presents a supplementary method of analysis by providing the design and results of a meta study on the environmental impact of lithium ion batteries. The study focuses on energy demand, and investigates its total impact for different cases considering 2nd life applications such as (C1) material recycling, (C2) repurposing and (C3) reuse. Required reprocessing methods such as remanufacturing of batteries lie at the basis of these 2nd life applications. Batteries are used in their 2nd lives for stationary energy storage (C2, repurpose) and electric vehicles (C3, reuse). The study results confirm that both of these 2nd life applications require less energy than the recycling of batteries at the end of their first life and the production of new batteries. The paper concludes by identifying future research areas in order to generate precise forecasts for 2nd life applications and their industrial dissemination.

scholarly journals Energy Performance Assessment of Innovative Building Solutions Coming from Construction and Demolition Waste Materials

Materials ◽  
2021 ◽  
Vol 14 (5) ◽  
pp. 1226
Author(s):  
Beatriz Fraga-De Cal ◽  
Antonio Garrido-Marijuan ◽  
Olaia Eguiarte ◽  
Beñat Arregi ◽  
Ander Romero-Amorrortu ◽  
...  
Keyword(s):  
Thermal Insulation ◽  
Energy Demand ◽  
Energy Savings ◽  
Flow Analysis ◽  
Weather Conditions ◽  
Energy Performance ◽  
Construction And Demolition Waste ◽  
The European Union ◽  
Demolition Waste ◽  
The Impact

Prefabricated solutions incorporating thermal insulation are increasingly adopted as an energy conservation measure for building renovation. The InnoWEE European project developed three technologies from Construction and Demolition Waste (CDW) materials through a manufacturing process that supports the circular economy strategy of the European Union. Two of them consisted of geopolymer panels incorporated into an External Thermal Insulation Composite System (ETICS) and a ventilated façade. This study evaluates their thermal performance by means of monitoring data from three pilot case studies in Greece, Italy, and Romania, and calibrated building simulation models enabling the reliable prediction of energy savings in different climates and use scenarios. Results showed a reduction in energy demand for all demo buildings, with annual energy savings up to 25% after placing the novel insulation solutions. However, savings are highly dependent on weather conditions since the panels affect cooling and heating loads differently. Finally, a parametric assessment is performed to assess the impact of insulation thickness through an energy performance prediction and a cash flow analysis.

scholarly journals Reducing environmental impacts from garments through best practice garment use and care, using the example of a Merino wool sweater

2021 ◽  
Author(s):  
Stephen G. Wiedemann ◽  
Leo Biggs ◽  
Quan V. Nguyen ◽  
Simon J. Clarke ◽  
Kirsi Laitala ◽  
...  
Keyword(s):  
Environmental Impacts ◽  
Energy Demand ◽  
Best Practice ◽  
Western Europe ◽  
Impact Category ◽  
Fashion Industry ◽  
Worst Case ◽  
Multiple Users ◽  
Washing Machines ◽  
The Impact

Abstract Purpose Garment production and use generate substantial environmental impacts, and the care and use are key determinants of cradle-to-grave impacts. The present study investigated the potential to reduce environmental impacts by applying best practices for garment care combined with increased garment use. A wool sweater is used as an example because wool garments have particular attributes that favour reduced environmental impacts in the use phase. Methods A cradle-to-grave life cycle assessment (LCA) was used to compare six plausible best and worst-case practice scenarios for use and care of a wool sweater, relative to current practices. These focussed on options available to consumers to reduce impacts, including reduced washing frequency, use of more efficient washing machines, reduced use of machine clothing dryers, garment reuse by multiple users, and increasing number of garment wears before disposal. A sixth scenario combined all options. Worst practices took the worst plausible alternative for each option investigated. Impacts were reported per wear in Western Europe for climate change, fossil energy demand, water stress and freshwater consumption. Results and discussion Washing less frequently reduced impacts by between 4 and 20%, while using more efficient washing machines at capacity reduced impacts by 1 to 6%, depending on the impact category. Reduced use of machine dryer reduced impacts by < 5% across all indicators. Reusing garments by multiple users increased life span and reduced impacts by 25–28% across all indicators. Increasing wears from 109 to 400 per garment lifespan had the largest effect, decreasing impacts by 60% to 68% depending on the impact category. Best practice care, where garment use was maximised and care practices focussed on the minimum practical requirements, resulted in a ~ 75% reduction in impacts across all indicators. Unsurprisingly, worst-case scenarios increased impacts dramatically: using the garment once before disposal increased GHG impacts over 100 times. Conclusions Wool sweaters have potential for long life and low environmental impact in use, but there are substantial differences between the best, current and worst-case scenarios. Detailed information about garment care and lifespans is needed to understand and reduce environmental impacts. Opportunities exist for consumers to rapidly and dramatically reduce these impacts. The fashion industry can facilitate this through garment design and marketing that promotes and enables long wear life and minimal care.

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