scholarly journals Distinct mitochondrial remodeling during early cardiomyocyte development in a human-based stem cell model

2021 ◽  
Author(s):  
Sepideh Mostafavi ◽  
Novin Balafkan ◽  
Ina Katrine Nitschke Pettersen ◽  
Gonzalo S. Nido ◽  
Richard Siller ◽  
...  

Post-mitotic tissues with high-energy demand rely on ATP generated by the mitochondrial respiratory chain through the process of oxidative phosphorylation (OXPHOS). There is common agreement that mitochondrial content and OXPHOS activity increase as cells exit from pluripotency state to meet the higher energy requirement of differentiated tissues such as heart. In this study, we examined the hypothesis that mitochondrial expansion during differentiation is necessary to compensate for higher energy demand in differentiated cells. We assessed mitochondrial and cellular metabolism during differentiation of human pluripotent stem cells to cardiac progenitors and further to functional cardiomyocytes. Contrary to expectations, we found that mitochondrial content decreased progressively during mesoderm differentiation. Nevertheless, we found that there was increased mitochondrial activity and higher levels of ATP-linked respiration, which we suggest more than compensate for the lower mitochondrial number. Our findings support a model whereby mitochondrial maturation during cardiomyocyte differentiation depends on increased efficiency of ATP generation through OXPHOS not increased mitochondrial biogenesis. Thus, the timing of the mitochondria expansion during cardiomyocyte differentiation will have to be revisited in light of these findings.

Author(s):  
Sepideh Mostafavi ◽  
Novin Balafkan ◽  
Ina Katrine Nitschke Pettersen ◽  
Gonzalo S. Nido ◽  
Richard Siller ◽  
...  

Given the considerable interest in using stem cells for modeling and treating disease, it is essential to understand what regulates self-renewal and differentiation. Remodeling of mitochondria and metabolism, with the shift from glycolysis to oxidative phosphorylation (OXPHOS), plays a fundamental role in maintaining pluripotency and stem cell fate. It has been suggested that the metabolic “switch” from glycolysis to OXPHOS is germ layer-specific as glycolysis remains active during early ectoderm commitment but is downregulated during the transition to mesoderm and endoderm lineages. How mitochondria adapt during these metabolic changes and whether mitochondria remodeling is tissue specific remain unclear. Here, we address the question of mitochondrial adaptation by examining the differentiation of human pluripotent stem cells to cardiac progenitors and further to differentiated mesodermal derivatives, including functional cardiomyocytes. In contrast to recent findings in neuronal differentiation, we found that mitochondrial content decreases continuously during mesoderm differentiation, despite increased mitochondrial activity and higher levels of ATP-linked respiration. Thus, our work highlights similarities in mitochondrial remodeling during the transition from pluripotent to multipotent state in ectodermal and mesodermal lineages, while at the same time demonstrating cell-lineage-specific adaptations upon further differentiation. Our results improve the understanding of how mitochondrial remodeling and the metabolism interact during mesoderm differentiation and show that it is erroneous to assume that increased OXPHOS activity during differentiation requires a simultaneous expansion of mitochondrial content.


2019 ◽  
Vol 97 ◽  
pp. 01042
Author(s):  
Anna Lis

The WHO report shows that air in the majority of cities in the world is polluted to a large extent. Air pollution is one of the basic environmental causes of premature deaths in the world. The main source of air pollution in cities is the low emission associated with fuel combustion to generate heat for buildings heating, communication and industry. The existing buildings in Poland are characterized by high energy and, consequently, ecological potential. The aim is to estimate predicted energetic and ecological effects of activities that adapt existing residential buildings to the requirements for the thermal protection of buildings in Poland and presenting the possibility of using renewable energy sources. The energy demand for heating buildings at 60-70 kWh/(m2rok) has been adopted. The calculations show that as a result of this adjustment, the energy demand for heating in residential buildings may decrease by an average of around 67% compared to 2011. Such actions will reduce the overall emissions of air pollution from households by reducing the energy requirement for heating apartments from about 30% to about 67%, depending on the type of pollutant.


Author(s):  
Harvey B. Sarnat ◽  
Laura Flores-Sarnat ◽  
Walter Hader ◽  
Luis Bello-Espinosa

Background:Repetitively discharging neurons in epileptic foci have a high energy requirement that might be demonstrated histochemically as increased mitochondrial enzymatic activity in brain resections for epilepsy in children.Materials and Methods:Frozen sections were studied histochemically of 10 brain resections from 7 epileptic children, 2 months to 17 years of age. None had mitochondrial disease. Three patients had tuberous sclerosis (TS) or hemimegalencephy (HME). Tissues included hippocampus and neocortex. Oxidative enzymes were studied for respiratory chain complexes I, II, IV, using the muscle biopsy protocol. In addition, immunoreactivities of α-B-crystallin and transmission electron microscopy (EM) were performed.Results:Oxidative activities were variable in adjacent neurons within a field: a minority were intense, adjacent to neurons with weaker mitochondrial activity exhibiting poor contrast of the soma because of similar oxidative activity in surrounding neuropil. Endothelium of vessels uniformly exhibits strong activity. Alpha-B-crystallin reactivity was strong at these foci. EM confirmed an abundance of neuronal mitochondria with normal cristae. In TS and HME, many dysplastic neurons showed intense activity; balloon cells had sparse activity.Conclusions:Histochemistry of mitochondrial oxidative enzymes reveals scattered and clustered neurons with stronger activities than others at epileptic foci. Such intensely staining neurons may be functionally “hypermetabolic” but they do not signify mitochondrial disease. Individual intensely stained neurons might be epileptogenic, but do not denote an epileptogenic field in the same manner as α-B-crystallin, which also was strongly reactive in these foci.


2020 ◽  
Author(s):  
Lissa Ventura-Antunes ◽  
Suzana Herculano-Houzel

AbstractNeuronal densities vary enormously across sites within a brain. Does the density of the capillary bed accompany the presumably larger energy requirement of sites with more neurons, or with larger neurons, or is energy supply constrained by a mostly homogeneous capillary bed? Here we find evidence for the latter across various sites in the mouse brain and show that as a result, the ratio of capillary cells per neuron, and thus presumably blood and energy supply per neuron, decreases uniformly with increasing neuronal density and therefore smaller average neuronal size across sites. Additionally, we find that local capillary density is also not correlated with local synapse densities, although there is a small but significant correlation between lower neuronal density (and therefore larger neuronal size) and more synapses per neuron within the restricted range of 6,500-9,500 across cortical sites. Further, local variations in the glial/neuron ratio are also not correlated with local variations in number of synapses per neuron or local synaptic densities. These findings suggest that it is not that larger neurons, neurons with more synapses, or even sites with more synapses demand more energy, but simply that larger (and thus fewer) neurons have more energy available per cell, and to its synapses as a whole, than smaller (and thus more numerous) neurons due to competition for limited resources supplied by a capillary bed of fairly homogeneous density throughout the brain.Significance StatementThe brain is an expensive organ and at rest already uses nearly as much energy as during sensory activation. To ultimately determine whether the high energy cost of the brain is driven by an unusually high energy demand by neurons or constrained by capillary density in the organ, we examine whether sites in the mouse brain with more neurons, larger neurons, or more synapses have more capillary supply, and find instead that capillary density is mostly homogeneous across brain structures. We propose that neurons are constrained to using what energy is available, with little evidence for adjustments according to local demand, which explains its high risk of ischemia and vulnerability to states of compromised metabolism, including normal aging.


Agronomy ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 422 ◽  
Author(s):  
Gabriele Cola ◽  
Luigi Mariani ◽  
Stefania Toscano ◽  
Daniela Romano ◽  
Antonio Ferrante

The ornamental plant production in greenhouses is widespread. A quantitative assessment of greenhouse energy consumption and its variability in space and time is strategic to improve the sustainability of the cultivation. The specific environmental features of the cultivation areas can strongly affect the sustainability of the production. A dynamic simulation model of greenhouse energy balance with an hourly time step was developed and parameterized for a state-of-the-art greenhouse to evaluate the heating requirements for cut-flower roses. This ornamental crop has been used as model species for its high energy requirement for flower production. The energy demand for rose production has been analyzed with an energy balance model with an hourly time step. After a preliminary analysis on the period 1973–2019, the final analysis was carried out on the 30-year period (1990–2019), representative of the current climate. Results show a gradient southwest–northeast of energy needs with relevant effects on economic and environmental sustainability. More specifically, four large sub-areas are identified, namely the central-southern Mediterranean (yearly requirements below 600 MJ m−2 year), the northern Mediterranean, and the area influenced by the mitigating effect of the Atlantic Ocean (600–1200), the central-European area (requirements of 1200–1800), and the Northern European area (above 1800).


2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Manuel J. Rodríguez ◽  
Margot Martínez-Moreno ◽  
Francisco J. Ortega ◽  
Nicole Mahy

Neurodegeneration is a complex process involving different cell types and neurotransmitters. A common characteristic of neurodegenerative disorders is the occurrence of a neuroinflammatory reaction in which cellular processes involving glial cells, mainly microglia and astrocytes, are activated in response to neuronal death. Microglia do not constitute a unique cell population but rather present a range of phenotypes closely related to the evolution of neurodegeneration. In a dynamic equilibrium with the lesion microenvironment, microglia phenotypes cover from a proinflammatory activation state to a neurotrophic one directly involved in cell repair and extracellular matrix remodeling. At each moment, the microglial phenotype is likely to depend on the diversity of signals from the environment and of its response capacity. As a consequence, microglia present a high energy demand, for which the mitochondria activity determines the microglia participation in the neurodegenerative process. As such, modulation of microglia activity by controlling microglia mitochondrial activity constitutes an innovative approach to interfere in the neurodegenerative process. In this review, we discuss the mitochondrial KATPchannel as a new target to control microglia activity, avoid its toxic phenotype, and facilitate a positive disease outcome.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Matthew Baxter ◽  
Maria Voronkov ◽  
Toryn Poolman ◽  
Gina Galli ◽  
Christian Pinali ◽  
...  

Efficient mitochondrial function is required in tissues with high energy demand such as the heart, and mitochondrial dysfunction is associated with cardiovascular disease. Expression of mitochondrial proteins is tightly regulated in response to internal and external stimuli. Here we identify a novel mechanism regulating mitochondrial content and function, through BUD23-dependent ribosome generation. BUD23 was required for ribosome maturation, normal 18S/28S stoichiometry and modulated the translation of mitochondrial transcripts in human A549 cells. Deletion of Bud23 in murine cardiomyocytes reduced mitochondrial content and function, leading to severe cardiomyopathy and death. We discovered that BUD23 selectively promotes ribosomal interaction with low GC-content 5’UTRs. Taken together we identify a critical role for BUD23 in bioenergetics gene expression, by promoting efficient translation of mRNA transcripts with low 5’UTR GC content. BUD23 emerges as essential to mouse development, and to postnatal cardiac function.


Reproduction ◽  
2000 ◽  
pp. 143-149 ◽  
Author(s):  
RM Sainz ◽  
RJ Reiter ◽  
JC Mayo ◽  
J Cabrera ◽  
DX Tan ◽  
...  

Pregnancy is a physiological state accompanied by a high energy demand of many bodily functions and an increased oxygen requirement. Because of the increased intake and utilization of oxygen, increased levels of oxidative stress would be expected. In the present study, the degree of lipid peroxidation was examined in different tissues from non-pregnant and pregnant rats after the delivery of their young. Melatonin and other indole metabolites are known to be direct free radical scavengers and indirect antioxidants. Thus the effect of pinealectomy at 1 month before pregnancy on the accumulation of lipid damage was investigated in non-pregnant and pregnant rats after the delivery of their young. Malonaldehyde and 4-hydroxyalkenal concentrations were measured in the lung, uterus, liver, brain, kidney, thymus and spleen from intact and pinealectomized pregnant rats soon after birth of their young and at 14 and 21 days after delivery. The same parameters were also evaluated in intact and pinealectomized non-pregnant rats. Shortly after delivery, lipid oxidative damage was increased in lung, uterus, brain, kidney and thymus of the mothers. No differences were detected in liver and spleen. Pinealectomy enhanced this effect in the uterus and lung. It is concluded that during pregnancy high levels of oxidative stress induce an increase in oxidative damage to lipids, which in some cases is inhibited by the antioxidative actions of pineal indoles.


2020 ◽  
Vol 9 (1) ◽  
pp. 386-398 ◽  
Author(s):  
Mahmood S. Jameel ◽  
Azlan Abdul Aziz ◽  
Mohammed Ali Dheyab

AbstractPlatinum nanoparticles (Pt NPs) have attracted interest in catalysis and biomedical applications due to their unique structural, optical, and catalytic properties. However, the conventional synthesis of Pt NPs using the chemical and physical methods is constrained by the use of harmful and costly chemicals, intricate preparation requirement, and high energy utilization. Hence, this review emphasizes on the green synthesis of Pt NPs using plant extracts as an alternative approach due to its simplicity, convenience, inexpensiveness, easy scalability, low energy requirement, environmental friendliness, and minimum usage of hazardous materials and maximized efficiency of the synthesis process. The underlying complex processes that cover the green synthesis (biosynthesis) of Pt NPs were reviewed. This review affirms the effects of different critical parameters (pH, reaction temperature, reaction time, and biomass dosage) on the size and shape of the synthesized Pt NPs. For instance, the average particle size of Pt NPs was reported to decrease with increasing pH, reaction temperature, and concentration of plant extract.


2021 ◽  
Vol 22 (11) ◽  
pp. 5628
Author(s):  
Valquíria Campos Alencar ◽  
Juliana de Fátima dos Santos Silva ◽  
Renata Ozelami Vilas Boas ◽  
Vinícius Manganaro Farnézio ◽  
Yara N. L. F. de Maria ◽  
...  

Autoinducer 2 (or AI-2) is one of the molecules used by bacteria to trigger the Quorum Sensing (QS) response, which activates expression of genes involved in a series of alternative mechanisms, when cells reach high population densities (including bioluminescence, motility, biofilm formation, stress resistance, and production of public goods, or pathogenicity factors, among others). Contrary to most autoinducers, AI-2 can induce QS responses in both Gram-negative and Gram-positive bacteria, and has been suggested to constitute a trans-specific system of bacterial communication, capable of affecting even bacteria that cannot produce this autoinducer. In this work, we demonstrate that the ethanologenic Gram-negative bacterium Zymomonas mobilis (a non-AI-2 producer) responds to exogenous AI-2 by modulating expression of genes involved in mechanisms typically associated with QS in other bacteria, such as motility, DNA repair, and nitrogen fixation. Interestingly, the metabolism of AI-2-induced Z. mobilis cells seems to favor ethanol production over biomass accumulation, probably as an adaptation to the high-energy demand of N2 fixation. This opens the possibility of employing AI-2 during the industrial production of second-generation ethanol, as a way to boost N2 fixation by these bacteria, which could reduce costs associated with the use of nitrogen-based fertilizers, without compromising ethanol production in industrial plants.


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