scholarly journals Modeling the Effects of Calcium Overload on Mitochondrial Ultrastructural Remodeling

2021 ◽  
Vol 11 (5) ◽  
pp. 2071
Author(s):  
Jasiel O. Strubbe-Rivera ◽  
Jiahui Chen ◽  
Benjamin A. West ◽  
Kristin N. Parent ◽  
Guo-Wei Wei ◽  
...  

Mitochondrial cristae are dynamic invaginations of the inner membrane and play a key role in its metabolic capacity to produce ATP. Structural alterations caused by either genetic abnormalities or detrimental environmental factors impede mitochondrial metabolic fluxes and lead to a decrease in their ability to meet metabolic energy requirements. While some of the key proteins associated with mitochondrial cristae are known, very little is known about how the inner membrane dynamics are involved in energy metabolism. In this study, we present a computational strategy to understand how cristae are formed using a phase-based separation approach of both the inner membrane space and matrix space, which are explicitly modeled using the Cahn–Hilliard equation. We show that cristae are formed as a consequence of minimizing an energy function associated with phase interactions which are subject to geometric boundary constraints. We then extended the model to explore how the presence of calcium phosphate granules, entities that form in calcium overload conditions, exert a devastating inner membrane remodeling response that reduces the capacity for mitochondria to produce ATP. This modeling approach can be extended to include arbitrary geometrical constraints, the spatial heterogeneity of enzymes, and electrostatic effects to mechanize the impact of ultrastructural changes on energy metabolism.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuangyao Wang ◽  
Chris G. Carter ◽  
Quinn P. Fitzgibbon ◽  
Basseer M. Codabaccus ◽  
Gregory G. Smith

AbstractThis is the first study in an aquatic ectotherm to combine a stoichiometric bioenergetic approach with an endpoint stochastic model to explore dietary macronutrient content. The combination of measuring respiratory gas (O2 and CO2) exchange, nitrogenous (ammonia and urea) excretion, specific dynamic action (SDA), metabolic energy substrate use, and whole-body protein synthesis in spiny lobster, Sagmariasus verreauxi, was examined in relation to dietary protein. Three isoenergetic feeds were formulated with varying crude protein: 40%, 50% and 60%, corresponding to CP40, CP50 and CP60 treatments, respectively. Total CO2 and ammonia excretion, SDA magnitude and coefficient, and protein synthesis in the CP60 treatment were higher compared to the CP40 treatment. These differences demonstrate dietary protein influences post-prandial energy metabolism. Metabolic use of each major energy substrate varied at different post-prandial times, indicating suitable amounts of high-quality protein with major non-protein energy-yielding nutrients, lipid and carbohydrate, are critical for lobsters. The average contribution of protein oxidation was lowest in the CP50 treatment, suggesting mechanisms underlying the most efficient retention of dietary protein and suitable dietary inclusion. This study advances understanding of how deficient and surplus dietary protein affects energy metabolism and provides approaches for fine-scale feed evaluation to support sustainable aquaculture.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Tawfik Yahya ◽  
Nur Azah Hamzaid ◽  
Sadeeq Ali ◽  
Farahiyah Jasni ◽  
Hanie Nadia Shasmin

AbstractA transfemoral prosthesis is required to assist amputees to perform the activity of daily living (ADL). The passive prosthesis has some drawbacks such as utilization of high metabolic energy. In contrast, the active prosthesis consumes less metabolic energy and offers better performance. However, the recent active prosthesis uses surface electromyography as its sensory system which has weak signals with microvolt-level intensity and requires a lot of computation to extract features. This paper focuses on recognizing different phases of sitting and standing of a transfemoral amputee using in-socket piezoelectric-based sensors. 15 piezoelectric film sensors were embedded in the inner socket wall adjacent to the most active regions of the agonist and antagonist knee extensor and flexor muscles, i. e. region with the highest level of muscle contractions of the quadriceps and hamstring. A male transfemoral amputee wore the instrumented socket and was instructed to perform several sitting and standing phases using an armless chair. Data was collected from the 15 embedded sensors and went through signal conditioning circuits. The overlapping analysis window technique was used to segment the data using different window lengths. Fifteen time-domain and frequency-domain features were extracted and new feature sets were obtained based on the feature performance. Eight of the common pattern recognition multiclass classifiers were evaluated and compared. Regression analysis was used to investigate the impact of the number of features and the window lengths on the classifiers’ accuracies, and Analysis of Variance (ANOVA) was used to test significant differences in the classifiers’ performances. The classification accuracy was calculated using k-fold cross-validation method, and 20% of the data set was held out for testing the optimal classifier. The results showed that the feature set (FS-5) consisting of the root mean square (RMS) and the number of peaks (NP) achieved the highest classification accuracy in five classifiers. Support vector machine (SVM) with cubic kernel proved to be the optimal classifier, and it achieved a classification accuracy of 98.33 % using the test data set. Obtaining high classification accuracy using only two time-domain features would significantly reduce the processing time of controlling a prosthesis and eliminate substantial delay. The proposed in-socket sensors used to detect sit-to-stand and stand-to-sit movements could be further integrated with an active knee joint actuation system to produce powered assistance during energy-demanding activities such as sit-to-stand and stair climbing. In future, the system could also be used to accurately predict the intended movement based on their residual limb’s muscle and mechanical behaviour as detected by the in-socket sensory system.


2016 ◽  
Vol 311 (2) ◽  
pp. H347-H363 ◽  
Author(s):  
Arata Fukushima ◽  
Osama Abo Alrob ◽  
Liyan Zhang ◽  
Cory S. Wagg ◽  
Tariq Altamimi ◽  
...  

Dramatic maturational changes in cardiac energy metabolism occur in the newborn period, with a shift from glycolysis to fatty acid oxidation. Acetylation and succinylation of lysyl residues are novel posttranslational modifications involved in the control of cardiac energy metabolism. We investigated the impact of changes in protein acetylation/succinylation on the maturational changes in energy metabolism of 1-, 7-, and 21-day-old rabbit hearts. Cardiac fatty acid β-oxidation rates increased in 21-day vs. 1- and 7-day-old hearts, whereas glycolysis and glucose oxidation rates decreased in 21-day-old hearts. The fatty acid oxidation enzymes, long-chain acyl-CoA dehydrogenase (LCAD) and β-hydroxyacyl-CoA dehydrogenase (β-HAD), were hyperacetylated with maturation, positively correlated with their activities and fatty acid β-oxidation rates. This alteration was associated with increased expression of the mitochondrial acetyltransferase, general control of amino acid synthesis 5 like 1 (GCN5L1), since silencing GCN5L1 mRNA in H9c2 cells significantly reduced acetylation and activity of LCAD and β-HAD. An increase in mitochondrial ATP production rates with maturation was associated with the decreased acetylation of peroxisome proliferator-activated receptor-γ coactivator-1α, a transcriptional regulator for mitochondrial biogenesis. In addition, hypoxia-inducible factor-1α, hexokinase, and phosphoglycerate mutase expression declined postbirth, whereas acetylation of these glycolytic enzymes increased. Phosphorylation rather than acetylation of pyruvate dehydrogenase (PDH) increased in 21-day-old hearts, accounting for the low glucose oxidation postbirth. A maturational increase was also observed in succinylation of PDH and LCAD. Collectively, our data are the first suggesting that acetylation and succinylation of the key metabolic enzymes in newborn hearts play a crucial role in cardiac energy metabolism with maturation. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/acetylation-control-of-energy-metabolism-in-newborn-hearts/ .


2013 ◽  
Vol 2 (3) ◽  
pp. 65
Author(s):  
A. G. Shakhov ◽  
D. V. Fedosov ◽  
L. Y. Sashnina ◽  
O. V. Kazimirov

<p>As a result of wide antibiotics, sulfonamides and other antimicrobial agents usage for the therapy of the animals with the bacterial infections caused by various causative agents including <em>Escherichia coli</em>, many microorganisms gained resistance to the chemotherapeutic agents. New combined drugs are being worked out during recent years, the components of which have various influence mechanisms on the bacterial cell that helps to provide resistance forming control. The results of the researches of the new antimicrobial agents, containing antibiotics in their composition, and non-antibiotic agent influence on the ultrastructure of <em>Escherichia coli</em> are represented in this study.</p> <p>5-hour <em>Escherichia coli 866</em> culture was processed by the drugs of the minimum bactericidal (Tylocolinum-0.39 µg/ml, Tetragold-6.25 µg/ml, Cidisept-o-25 µg/ml) and 4-time concentrations during 3 hours. Samples and control culture (without drugs) were fixed by the 2.5% glutaricdialdehyde on the s-Collidine Buffer, dehydrated in the ethanol with rising concentration, filled in epoxies. Ultrathin slices were stained by 2% water solution of uranyl acetate and lead citrate for 10 minutes. Then they were examined with the use of the electron microscope JEM-100 CX II by JEOL.</p> <p>The research showed deep ultrastructural changes in <em>Escherichia coli</em> cells under the antimicrobial agent influence determined by synergistic effect of combined Tylocolinum and Tetragold drugs components, possessing various bacteria influencing mechanisms, and aldehyde that is a component of Cidisept-o.</p> The electron microscopy usage allows to get unique information about the impact consequences of the traditional improved drugs and new drugs with antimicrobial activity on the bacterial infectious agents.


Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1991
Author(s):  
Janine Mett

Alzheimer’s disease (AD), the most common cause of dementia in the elderly population, is closely linked to a dysregulated cerebral lipid homeostasis and particular changes in brain fatty acid (FA) composition. The abnormal extracellular accumulation and deposition of the peptide amyloid-β (Aβ) is considered as an early toxic event in AD pathogenesis, which initiates a series of events leading to neuronal dysfunction and death. These include the induction of neuroinflammation and oxidative stress, the disruption of calcium homeostasis and membrane integrity, an impairment of cerebral energy metabolism, as well as synaptic and mitochondrial dysfunction. Dietary medium chain fatty acids (MCFAs) and polyunsaturated ω-3-fatty acids (ω-3-PUFAs) seem to be valuable for disease modification. Both classes of FAs have neuronal health-promoting and cognition-enhancing properties and might be of benefit for patients suffering from mild cognitive impairment (MCI) and AD. This review summarizes the current knowledge about the molecular mechanisms by which MCFAs and ω-3-PUFAs reduce the cerebral Aβ deposition, improve brain energy metabolism, and lessen oxidative stress levels.


2021 ◽  
Vol 8 ◽  
Author(s):  
Daniella Corporan ◽  
Ana Segura ◽  
Muralidhar Padala

Introduction: Mitral regurgitation (MR) imposes volume overload on the left ventricle (LV) and elevates wall stress, triggering its adverse remodeling. Pronounced LV dilation, minimal wall thinning, and a gradual decline in cardiac ejection fraction (EF) are observed. The structural changes in the myocardium that define these gross, organ level remodeling are not known. Cardiomyocyte elongation and slippage have both been hypothesized, but neither are confirmed, nor are the changes to the cardiomyocyte structure known. Using a rodent model of MR, we used immunohistochemistry and transmission electron microscopy (TEM) to describe the ultrastructural remodeling of the cardiomyocyte.Methods: Twenty-four male Sprague-Dawley rats (350–400 g) were assigned to two groups: group (1) rats induced with severe MR (n = 18) and group (2) control rats that were healthy and age and weight matched (n = 6). MR was induced in the beating heart using a 23-G ultrasound-guided, transapical needle to perforate the anterior mitral leaflet, and the rats were followed to 2, 10, and 20 weeks (n = 6/time-point). Echocardiography was performed to quantify MR severity and to measure LV volume and function at each time-point. Explanted myocardial tissue were examined with TEM and immunohistochemistry to investigate the ultrastructural changes.Results: MR induced rapid and significant increase in end-diastolic volume (EDV), with a 50% increase by 2 weeks, compared with control. Rise in end-systolic volume (ESV) was more gradual; however, by 20 weeks, both EDV and ESV in MR rats were increased by 126% compared with control. A significant decline in EF was measured at 10 weeks of MR. At the ultrastructural level, as early as 2 weeks after MR, cardiomyocyte elongation and increase in cross-sectional area were observed. TEM depicted sarcomere shortening, with loss of Z-line and I-band. Desmin, a cytoskeletal protein that is uniformly distributed along the length of the cardiomyocyte, was disorganized and localized to the intercalated disc, in the rats induced with MR and not in the controls. In the rats with MR, the linear registry of the mitochondrial arrangement along the sarcomeres was lost, with mitochondrial fragmentation, aggregation around the nucleus, and irregularities in the cristae.Discussion: In the setting of chronic mitral regurgitation, LV dilatation occured by cardiomyocyte elongation, which manifests at the subcellular level as distinct ultrastructural alterations of the sarcomere, cytoskeleton, and mitochondria. Since the cytoskeleton not only provides tensegrity but has functional consequences on myocyte function, further investigation into the impact of cytoskeletal remodeling on progressive heart failure or recovery of function upon correcting the valve lesion are needed.


1992 ◽  
Vol 11 (3) ◽  
pp. 140-146 ◽  
Author(s):  
C. Lennmarken ◽  
S. Skullman ◽  
M. Wirén ◽  
E. Vinnars ◽  
J. Larsson

Antioxidants ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 186 ◽  
Author(s):  
Hakjoo Lee ◽  
Yisang Yoon

The maintenance of mitochondrial energetics requires the proper regulation of mitochondrial morphology, and vice versa. Mitochondrial dynamins control mitochondrial morphology by mediating fission and fusion. One of them, optic atrophy 1 (OPA1), is the mitochondrial inner membrane remodeling protein. OPA1 has a dual role in maintaining mitochondrial morphology and energetics through mediating inner membrane fusion and maintaining the cristae structure. OPA1 is expressed in multiple variant forms through alternative splicing and post-translational proteolytic cleavage, but the functional differences between these variants have not been completely understood. Recent studies generated new information regarding the role of OPA1 cleavage. In this review, we will first provide a brief overview of mitochondrial membrane dynamics by describing fission and fusion that are mediated by mitochondrial dynamins. The second part describes OPA1-mediated fusion and energetic maintenance, the role of OPA1 cleavage, and a new development in OPA1 function, in which we will provide new insight for what OPA1 does and what proteolytic cleavage of OPA1 is for.


Sensors ◽  
2019 ◽  
Vol 19 (10) ◽  
pp. 2280 ◽  
Author(s):  
Sören Vogel ◽  
Hamza Alkhatib ◽  
Johannes Bureick ◽  
Rozhin Moftizadeh ◽  
Ingo Neumann

Georeferencing is an indispensable necessity regarding operating with kinematic multi-sensor systems (MSS) in various indoor and outdoor areas. Information from object space combined with various types of prior information (e.g., geometrical constraints) are beneficial especially in challenging environments where common solutions for pose estimation (e.g., global navigation satellite system or external tracking by a total station) are inapplicable, unreliable or inaccurate. Consequently, an iterated extended Kalman filter is used and a general georeferencing approach by means of recursive state estimation is introduced. This approach is open to several types of observation inputs and can deal with (non)linear systems and measurement models. The capability of using both explicit and implicit formulations of the relation between states and observations, and the consideration of (non)linear equality and inequality state constraints is a special feature. The framework presented is evaluated by an indoor kinematic MSS based on a terrestrial laser scanner. The focus here is on the impact of several different combinations of applied state constraints and the dependencies of two classes of inertial measurement units (IMU). The results presented are based on real measurement data combined with simulated IMU measurements.


2020 ◽  
Vol 96 (8) ◽  
pp. 1076-1083
Author(s):  
Dajana Todorović ◽  
Larisa Ilijin ◽  
Marija Mrdaković ◽  
Milena Vlahović ◽  
Anja Grčić ◽  
...  

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