scholarly journals Regulation of ATP supply during muscle contraction: theoretical studies

1998 ◽  
Vol 330 (3) ◽  
pp. 1189-1195 ◽  
Author(s):  
Bernard KORZENIEWSKI

The dynamic computer model of oxidative phosphorylation developed previously and successfully tested for large-scale changes in fluxes and metabolite concentrations was used to study the question of how the rate of ATP production by oxidative phosphorylation is adjusted to meet the energy demand during muscle contraction, which causes a great increase in ATP consumption in relation to the resting state. The changes in the respiration rate and ATP/ADP ratio after the onset of maximal work measured experimentally were compared with simulated changes in the respiration rate and ATP/ADP in several different cases, assuming direct activation of different steps by an external effector. On the basis of the computer simulations performed, it was possible to conclude which enzymes/metabolic blocks should be directly activated to cause the experimentally observable changes in fluxes and metabolite concentrations. The theoretical results obtained suggest that the parallel direct activation of actinomyosin-ATP-ase and oxidative phosphorylation by an external effector (for example calcium ions) is the main mechanism responsible for fitting of ATP production to ATP consumption, while the negative feedback via an increase in ADP concentration (decrease in ATP/ADP), which indirectly activates the ATP supply, plays only a minor role. Additionally, the conclusion is drawn that most of the oxidative phosphorylation steps should be directly activated in order to explain the observed changes in the respiration rate and ATP/ADP ratio (and also in other parameters) during muscle contraction. It is suggested that there should exist a universal external activator/regulatory mechanism which causes a parallel stimulation of different enzymes/processes. A possible nature of such an activator is shortly discussed.

2007 ◽  
Vol 292 (1) ◽  
pp. C52-C58 ◽  
Author(s):  
Anne Devin ◽  
Michel Rigoulet

This review focuses on the different mechanisms involved in the adjustment of mitochondrial ATP production to cellular energy demand. The oxidative phosphorylation steady state at constant mitochondrial enzyme content can vary in response to energy demand. However, such an adaptation is tightly linked to a modification in both oxidative phosphorylation yield and phosphate potential and is obviously very limited in eukaryotic cells. We describe the three main mechanisms involved in mitochondrial response to energy demand. In heart cells, a short-term adjustment can be reached mainly through metabolic signaling via phosphotransfer networks by the compartmentalized energy transfer and signal transmission. In such a complex regulatory mechanism, Ca2+signaling participates in activation of matricial dehydrogenases as well as mitochondrial ATP synthase. These processes allow a large increase in ATP production rate without an important modification in thermodynamic forces. For a long-term adaptation, two main mechanisms are involved: modulation of the mitochondrial enzyme content as a function of energy demand and/or kinetic regulation by covalent modifications (phosphorylations) of some respiratory chain complex subunits. Regardless of the mechanism involved (kinetic regulation by covalent modification or adjustment of mitochondrial enzyme content), the cAMP signaling pathway plays a major role in molecular signaling, leading to the mitochondrial response. We discuss the energetic advantages of these mechanisms.


Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 470
Author(s):  
Rafael Mesquita ◽  
Alessandro Gaviraghi ◽  
Renata Gonçalves ◽  
Marcos Vannier-Santos ◽  
Julio Mignaco ◽  
...  

Flight dispersal represents a key aspect of the evolutionary and ecological success of insects, allowing escape from predators, mating, and colonization of new niches. The huge energy demand posed by flight activity is essentially met by oxidative phosphorylation (OXPHOS) in flight muscle mitochondria. In insects, mitochondrial ATP supply and oxidant production are regulated by several factors, including the energy demand exerted by changes in adenylate balance. Indeed, adenylate directly regulates OXPHOS by targeting both chemiosmotic ATP production and the activities of specific mitochondrial enzymes. In several organisms, cytochrome c oxidase (COX) is regulated at transcriptional, post-translational, and allosteric levels, impacting mitochondrial energy metabolism, and redox balance. This review will present the concepts on how COX function contributes to flying insect biology, focusing on the existing examples in the literature where its structure and activity are regulated not only by physiological and environmental factors but also how changes in its activity impacts insect biology. We also performed in silico sequence analyses and determined the structure models of three COX subunits (IV, VIa, and VIc) from different insect species to compare with mammalian orthologs. We observed that the sequences and structure models of COXIV, COXVIa, and COXVIc were quite similar to their mammalian counterparts. Remarkably, specific substitutions to phosphomimetic amino acids at critical phosphorylation sites emerge as hallmarks on insect COX sequences, suggesting a new regulatory mechanism of COX activity. Therefore, by providing a physiological and bioenergetic framework of COX regulation in such metabolically extreme models, we hope to expand the knowledge of this critical enzyme complex and the potential consequences for insect dispersal.


Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 532
Author(s):  
Dorota Wesół-Kucharska ◽  
Dariusz Rokicki ◽  
Aleksandra Jezela-Stanek

Mitochondrial diseases are a heterogeneous group of diseases resulting from energy deficit and reduced adenosine triphosphate (ATP) production due to impaired oxidative phosphorylation. The manifestation of mitochondrial disease is usually multi-organ. Epilepsy is one of the most common manifestations of diseases resulting from mitochondrial dysfunction, especially in children. The onset of epilepsy is associated with poor prognosis, while its treatment is very challenging, which further adversely affects the course of these disorders. Fortunately, our knowledge of mitochondrial diseases is still growing, which gives hope for patients to improve their condition in the future. The paper presents the pathophysiology, clinical picture and treatment options for epilepsy in patients with mitochondrial disease.


Genetics ◽  
2001 ◽  
Vol 159 (3) ◽  
pp. 929-938
Author(s):  
G D Clark-Walker ◽  
X J Chen

Abstract Loss of mtDNA or mitochondrial protein synthesis cannot be tolerated by wild-type Kluyveromyces lactis. The mitochondrial function responsible for ρ0-lethality has been identified by disruption of nuclear genes encoding electron transport and F0-ATP synthase components of oxidative phosphorylation. Sporulation of diploid strains heterozygous for disruptions in genes for the two components of oxidative phosphorylation results in the formation of nonviable spores inferred to contain both disruptions. Lethality of spores is thought to result from absence of a transmembrane potential, ΔΨ, across the mitochondrial inner membrane due to lack of proton pumping by the electron transport chain or reversal of F1F0-ATP synthase. Synergistic lethality, caused by disruption of nuclear genes, or ρ0-lethality can be suppressed by the atp2.1 mutation in the β-subunit of F1-ATPase. Suppression is viewed as occurring by an increased hydrolysis of ATP by mutant F1, allowing sufficient electrogenic exchange by the translocase of ADP in the matrix for ATP in the cytosol to maintain ΔΨ. In addition, lethality of haploid strains with a disruption of AAC encoding the ADP/ATP translocase can be suppressed by atp2.1. In this case suppression is considered to occur by mutant F1 acting in the forward direction to partially uncouple ATP production, thereby stimulating respiration and relieving detrimental hyperpolarization of the inner membrane. Participation of the ADP/ATP translocase in suppression of ρ0-lethality is supported by the observation that disruption of AAC abolishes suppressor activity of atp2.1.


2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Sagartirtha Sarkar ◽  
Santanu Rana

Cardiac tissue engineering is an interdisciplinary field that engineers modulation of viable molecular milieu to restore, maintain or improve heart function. Myocardial workload (energy demand) and energy substrate availability (supply) are in continual flux to maintain specialized cellular processes, yet the heart has a limited capacity for substrate storage and utilization during pathophysiological conditions. Damage to heart muscle, acute or chronic, leads to dysregulation of cardiac metabolic processes associated with gradual but progressive decline in mitochondrial respiratory pathways resulting in diminished ATP production. The Peroxisome Proliferator Activated Receptor Alpha ( PPARα ) is known to regulate fatty acid to glucose metabolic balance as well as mitochondrial structural integrity. In this study, a non-canonical pathway of PPARα was analyzed by cardiomyocyte targeted PPARα overexpression during cardiac hypertrophy that showed significant downregulation in p53 acetylation as well as GSK3β activation levels. Targeted PPARα overexpression during hypertrophy resulted in restoration of mitochondrial structure and function along with significantly improved mitochondrial ROS generation and membrane potential. This is the first report of myocyte targeted PPARα overexpression in hypertrophied myocardium that results in an engineered heart with significantly improved function with increased muscle mitochondrial endurance and reduced mitochondrial apoptotic load, thus conferring a greater resistance to pathological stimuli within cardiac microenvironment.


2005 ◽  
Vol 23 (10) ◽  
pp. 3365-3373 ◽  
Author(s):  
J. Birn ◽  
M. Hesse

Abstract. Magnetic reconnection is the crucial process in the release of magnetic energy previously stored in the magnetotail in association with substorms. However, energy transfer and dissipation in the vicinity of the reconnection site is only a minor part of the energy conversion. We discuss the energy release, transport, and conversion based on large-scale resistive MHD simulations of magnetotail dynamics and more localized full particle simulations of reconnection. We address in particular, where the energy is released, how it propagates and where and how it is converted from one form into another. We find that Joule (or ohmic) dissipation plays only a minor role in the overall energy transfer. Bulk kinetic energy, although locally significant in the outflow from the reconnection site, plays a more important role as mediator or catalyst in the transfer between magnetic and thermal energy. Generator regions with potential auroral consequences are located primarily off the equatorial plane in the boundary regions of the plasma sheet.


Author(s):  
Raffaele Capuano ◽  
Thomas Fend ◽  
Bernhard Hoffschmidt ◽  
Robert Pitz-Paal

Due to the continuous global increase in energy demand, Concentrated Solar Power (CSP) represents an excellent alternative, or add-on to existing systems for the production of energy on a large scale. In some of these systems, the Solar Power Tower plants (SPT), the conversion of solar radiation into heat occurs in certain components defined as solar receivers, placed in correspondence of the focus of the reflected sunlight. In a particular type of solar receivers, defined as volumetric, the use of porous materials is foreseen. These receivers are characterized by a porous structure called absorber. The latter, hit by the reflected solar radiation, transfers the heat to the evolving fluid, generally air subject to natural convection. The proper design of these elements is essential in order to achieve high efficiencies, making such structures extremely beneficial for the overall performances of the energy production process. In the following study, a parametric analysis and an optimized characterization of the structure have been performed with the use of self-developed numerical models. The knowledge and results gained through this study have been used to define an optimization path in order to improve the absorber microstructure, starting from the current in-house state-of-the-art technology until obtaining a new advanced geometry.


Author(s):  
Jianfeng Xu ◽  
Basel Abdalla ◽  
Ayman Eltaher ◽  
Paul Jukes

The increasing energy demand has promoted the interest in exploration and field development in the Arctic waters, which holds one quarter of the world’s petroleum reserves. The harsh conditions and fragile environment in the arctic region introduce many challenges to a sustainable development of these resources. One of the key challenges is the engineering consideration of warm pipelines installed in permafrost areas; found mainly in shallow waters and shore crossings. Evaluations have to be made during the pipeline design to avoid significant thaw settlement and large-scale permafrost degrading. In this paper, a three-dimensional (3D) finite element (FE) model was developed to study the interaction between buried pipelines transporting warm hydrocarbons and the surrounding permafrost. This interaction is a combination of several mechanisms: heat transfer from the pipeline, results in permafrost thawing and formation of thaw bulb around the pipeline. Consequently, the thaw settlement of soil beneath the pipeline base results in bending strains in the pipe wall. For safe operations, the pipe should be designed so that the induced strains do not exceed the ultimate limit state conditions. The developed model helps in accurate prediction of pipe strains by using finite element continuum modeling method as opposed to the more commonly used discrete (springs) modeling and hand calculations. It also assesses the real size of the thaw bulb and the corresponding settlement at any time, thus preventing an over-conservative design.


2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Mariangela Marrone ◽  
Rita Maria Laura La Rovere ◽  
Simone Guarnieri ◽  
Ester Sara Di Filippo ◽  
Giovanni Monaco ◽  
...  

Sarcopenia is the age-related loss of skeletal muscle mass, strength, and function. It is associated with regenerative difficulties by satellite cells, adult muscle stem cells, and alteration of oxidative management, mainly the increase in superoxide anions (O2•−). We aimed to investigate the relation between regenerative deficit in elderly and increase in O2•− production along with mitochondrial alterations. Myoblasts and myotubes from skeletal muscle of young and elderly healthy subjects (27.8 ± 6 and 72.4 ± 6.5 years old) were measured: (1) superoxide dismutase activity and protein content, (2) mitochondrial O2•− production levels, (3) O2•− production variability, and (4) mitochondrial bioenergetic profile. Compared to young myoblasts, elderly myoblasts displayed decreased SOD2 protein expression, elevated mitochondrial O2•− baseline levels, and decreased oxidative phosphorylation and glycolysis. Additionally, elderly versus young myotubes showed elevated mitochondrial O2•− levels when stressed with N-acetyl cysteine or high glucose and higher glycolysis despite showing comparable oxidative phosphorylation levels. Altogether, the elderly may have less metabolic plasticity due to the impaired mitochondrial function caused by O2•−. However, the increased energy demand related to the differentiation process appears to activate compensatory mechanisms for the partial mitochondrial dysfunction.


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