scholarly journals Systems modeling predicts that mitochondria ER contact sites regulate the postsynaptic energy landscape

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
A. Leung ◽  
D. Ohadi ◽  
G. Pekkurnaz ◽  
P. Rangamani
Keyword(s):  
Atp Hydrolysis ◽  
Energy State ◽  
Reaction Diffusion ◽  
Spatiotemporal Model ◽  
Atp Production ◽  
Contact Sites ◽  
Reaction Diffusion Model ◽  
Intracellular Organelles ◽  
Atp Generation

AbstractSpatiotemporal compartmentation of calcium dynamics is critical for neuronal function, particularly in postsynaptic spines. This exquisite level of Ca2+ compartmentalization is achieved through the storage and release of Ca2+ from various intracellular organelles particularly the endoplasmic reticulum (ER) and the mitochondria. Mitochondria and ER are established storage organelles controlling Ca2+ dynamics in neurons. Mitochondria also generate a majority of energy used within postsynaptic spines to support the downstream events associated with neuronal stimulus. Recently, high resolution microscopy has unveiled direct contact sites between the ER and the mitochondria (MERCs), which directly channel Ca2+ release from the ER into the mitochondrial membrane. In this study, we develop a computational 3D reaction-diffusion model to investigate the role of MERCs in regulating Ca2+ and ATP dynamics. This spatiotemporal model accounts for Ca2+ oscillations initiated by glutamate stimulus of metabotropic and ionotropic glutamate receptors and Ca2+ changes in four different compartments: cytosol, ER, mitochondria, and the MERC microdomain. Our simulations predict that the organization of these organelles and inter-organellar contact sites play a key role in modulating Ca2+ and ATP dynamics.We further show that the crosstalk between geometry (mitochondria and MERC) and metabolic parameters (cytosolic ATP hydrolysis, ATP generation) influences the neuronal energy state. Our findings shed light on the importance of organelle interactions in predicting Ca2+ dynamics in synaptic signaling. Overall, our model predicts that a combination of MERC linkage and mitochondria size is necessary for optimal ATP production in the cytosol.

scholarly journals Deciphering the postsynaptic calcium-mediated energy homeostasis through mitochondria-endoplasmic reticulum contact sites using systems modeling

2020 ◽  
Author(s):  
A. Leung ◽  
D. Ohadi ◽  
G. Pekkurnaz ◽  
P. Rangamani
Keyword(s):  
Endoplasmic Reticulum ◽  
Energy Homeostasis ◽  
Atp Hydrolysis ◽  
Energy State ◽  
Reaction Diffusion ◽  
Differential Distribution ◽  
Spatiotemporal Model ◽  
Atp Production ◽  
Contact Sites ◽  
Reaction Diffusion Model

AbstractSpatiotemporal compartmentation of calcium dynamics is critical for neuronal function, particularly in post-synaptic spines. This exquisite level of Ca2+ compartmentalization is achieved through the storage and release of Ca2+ from various intracellular organelles particularly the endoplasmic reticulum (ER) and the mitochondria. Mitochondria and ER are established storage organelles controlling Ca2+ dynamics in neurons. Mitochondria also generate a majority of energy used within postsynaptic spines to support the downstream events associated with neuronal stimulus. Recently, high resolution microscopy has unveiled direct contact sites between the ER and the mitochondria, which directly channel Ca2+ release from the ER into the mitochondrial membrane. In this study, we develop a computational 3D reaction-diffusion model to investigate the role of MERCs in regulating Ca2+ and ATP dynamics. This spatiotemporal model accounts for Ca2+ oscillations initiated by glutamate stimulus of metabotropic and ionotropic glutamate receptors and Ca2+ changes in four different compartments: cytosol, ER, mitochondria, and the MERC microdomain. Our simulations predict that the organization of these organelles and differential distribution of key Ca2+ channels such as IP3 receptor and ryanodine receptor modulate Ca2+ dynamics in response to different stimuli. We further show that the crosstalk between geometry (mitochondria and MERC) and metabolic parameters (cytosolic ATP hydrolysis, ATP generation) influences the cellular energy state. Our findings shed light on the importance of organelle interactions in predicting Ca2+ dynamics in synaptic signaling. Overall, our model predicts that a combination of MERC linkage and mitochondria size is necessary for optimal ATP production in the cytosol.

scholarly journals Reaction-diffusion model as framework for understanding the role of riboflavin in “eye defence” formulations

RSC Advances ◽  
2020 ◽  
Vol 10 (25) ◽  
pp. 14965-14971
Author(s):  
Francesca Di Nezza ◽  
Ciro Caruso ◽  
Ciro Costagliola ◽  
Luigi Ambrosone
Keyword(s):  
Diffusion Model ◽  
Reaction Diffusion ◽  
Eye Drops ◽  
Reaction Diffusion Model ◽  
Visible Spectra ◽  
Uv Visible

Analysis of UV-visible spectra, performed on commercial riboflavin-based eye drops, showed that absorbance is a saturating function of vitamin concentration.

Cardiac expression of adenine nucleotide translocase-1 in transgenic mice overexpressing bovine GH

2007 ◽  
Vol 194 (3) ◽  
pp. 521-527 ◽  
Author(s):  
Fausto Bogazzi ◽  
Francesco Raggi ◽  
Federica Ultimieri ◽  
Dania Russo ◽  
Antonella Manariti ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Transgenic Mice ◽  
Adenine Nucleotide ◽  
Adenine Nucleotide Translocase ◽  
Common Finding ◽  
Atp Production ◽  
Tissue Levels ◽  
Atp Generation ◽  
Gh Excess

Heart hypertrophy is a common finding of acromegaly, a syndrome due to GH excess. Impairment of adenine nucleotide translocase-1 (ANT-1) gene, the main mitochondrial ADP/ATP exchanger, leads to cardiac hypertrophy. The aim of the study was to evaluate cardiac expression and the functional role of ANT-1 in 1- to 12-month-old transgenic mice overexpressing bovine GH (acromegalic mice, Acro) and littermate controls (wild-type mice, Wt). GH specificity of protein degree variation was assessed treating Acro with pegvisomant, a GH receptor competitor. Tissue levels of ANT-1, NF-κB, ATP, and lactic acid were evaluated by western blot, bioluminescence, and Fourier transform infrared spectroscopy respectively. The degree of ANT-1 expression was higher in 1-month-old Acro than in Wt (47±5% OD vs 33±4% OD, P<0 01). On the contrary, ANT-1 expression was lower in 3- to 12-month-old Acro than in Wt (P<0 03). Changes in ANT-1 expression were associated with consistent changes of cellular ATP content, increasing at 1 month (P<0 05) and reducing thereafter in Acro when compared with Wt (P<0 04). Treatment with pegvisomant abolished ANT-1 and ATP changes observed in 1- and 3-month-old Acro, thus supporting a GH-dependent mechanism. Reduced ATP generation in hypertrophied hearts of older Acro was associated with increased lactic acid levels suggesting that part of energy was due to glycolysis. Variations in ANT-1 expression were linked to GH through changes in NF-κB, the levels of which changed accordingly. In conclusion, 1-month-old acromegalic mice had increased ANT-1 expression and higher degree of ATP production. Long-standing disease was associated with a consistent reduction of ANT-1 and ATP tissue levels, which became GH-independent in older animals. This study demonstrated a direct effect of GH on key proteins involved in energy metabolism of acromegalic hearts.

Role of dark excitations in the nonequilibrium condensation of exciton polaritons in optically-pumped organic single crystal microcavities

2015 ◽  
Vol 29 (22) ◽  
pp. 1550157 ◽  
Author(s):  
Svitlana Zaster ◽  
Eric R. Bittner
Keyword(s):  
Reaction Diffusion ◽  
Optically Pumped ◽  
Reaction Diffusion Model ◽  
Exciton Polaritons ◽  
Organic Single Crystal ◽  
Dielectric Mirrors ◽  
Dynamical Regimes ◽  
Nonequilibrium Condensation ◽  
External Driving

We present a reaction/diffusion model for the formation of a lower polariton condensate in a microcavity containing an organic semiconducting molecular crystalline film. Our model–based upon an anthracene film sandwiched between two reflecting dielectric mirrors–consists of three coupled fields corresponding to a gas of excitons created by an external driving pulse, a reservoir of dark states formed by the nonemissive decay of excitons in to nearby electronic states, and a lower polariton condensate. We show that at finite temperature, the presence of the dark reservoir can augment the exciton population such that a lower critical pumping threshold is required to achieve the critical exciton densities required to sustain a stable condensate population. Using linear-stability analysis, we show that a variety of dynamical regimes can emerge depending upon the characteristics of the cavity and the lattice temperature.

scholarly journals Sarcoplasmic reticulum–mitochondrial through-space coupling in skeletal muscleThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 34 (3) ◽  
pp. 389-395 ◽  
Author(s):  
Robert T. Dirksen
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Calcium Release ◽  
Atp Hydrolysis ◽  
Peer Review Process ◽  
Muscle Relaxation ◽  
Structural Basis ◽  
Atp Production ◽  
Atp Generation ◽  
Selection Of

The skeletal muscle contractile machine is fueled by both calcium and ATP. Calcium ions activate the contractile machinery by binding to troponin C and relieving troponin-tropomyosin inhibition of actinomyosin interaction. ATP binding to myosin during the contractile cycle results in myosin detachment from actin, and energy liberated from subsequent ATP hydrolysis is then used to drive the next contractile cycle. ATP is also used to lower myoplasmic calcium levels during muscle relaxation. Thus, muscle contractility is intimately linked to the proper control of sarcomeric Ca2+ delivery and (or) removal and ATP generation and (or) utilization. In skeletal muscle, the sarcoplasmic reticulum (SR) is the primary regulator of calcium storage, release, and reuptake, while glycolysis and the mitochondria are responsible for cellular ATP production. However, the SR and mitochondrial function in muscle are not independent, as calcium uptake into the mitochondria increases ATP production by stimulating oxidative phosphorylation and mitochondrial ATP production, and production and (or) detoxification of reactive oxygen and nitrogen species (ROS/RNS), in turn, modulates SR calcium release and reuptake. Close spatial Ca2+/ATP/ROS/RNS communication between the SR and mitochondria is facilitated by the structural attachment of mitochondria to the calcium release unit (CRU) by 10 nm of electron-dense tethers. The resultant anchoring of mitochondria to the CRU provides a structural basis for maintaining bidirectional SR–mitochondrial through-space communication during vigorous contraction. This review will consider the degree to which this structural link enables privileged or microdomain communication between the SR and mitochondria in skeletal muscle.

scholarly journals Nonclassical Kinetics in Constrained Geometries: Initial Distribution Effects

1998 ◽  
Vol 08 (05) ◽  
pp. 853-868 ◽  
Author(s):  
K. Lindenberg ◽  
A. H. Romero ◽  
J. M. Sancho
Keyword(s):  
Initial Density ◽  
Reaction Diffusion ◽  
Initial Distribution ◽  
Density Fluctuations ◽  
Time Behavior ◽  
Numerical Work ◽  
Irreversible Reaction ◽  
Long Wavelength ◽  
Reaction Diffusion Model

We present a detailed study of the effects of the initial distribution on the kinetic evolution of the irreversible reaction A+B→0 in one dimension. Our analytic as well as numerical work is based on a reaction–diffusion model of this reaction. We focus on the role of initial density fluctuations in the creation of the macroscopic patterns that lead to the well-known kinetic anomalies in this system. In particular, we discuss the role of the long wavelength components of the initial fluctuations in determining the long-time behavior of the system. We note that the frequently studied random initial distribution is but one of a variety of possible distributions leading to interesting anomalous behavior. Our discussion includes an initial distribution with correlated A-B pairs and one in which the initial distribution forms a fractal pattern. The former is an example of a distribution whose long wavelength components are suppressed, while the latter exemplifies one whose long wavelength components are enhanced, relative to those of the random distribution.

scholarly journals The Drosophila photoreceptor as a model system for studying signalling at membrane contact sites

2016 ◽  
Vol 44 (2) ◽  
pp. 447-451 ◽  
Author(s):  
Shweta Yadav ◽  
Shamshad Cockcroft ◽  
Padinjat Raghu
Keyword(s):  
Membrane Composition ◽  
Contact Site ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Physiological Processes ◽  
Specific Proteins ◽  
Intracellular Organelles ◽  
Membrane Contact ◽  
Cellular Compartments

Several recent studies have demonstrated the existence of membrane contact sites (MCS) between intracellular organelles in eukaryotic cells. Recent exciting studies have also demonstrated the existence of biomolecular interactions at these contact sites in mediating changes in the membrane composition of the cellular compartments. However, the role of such contact sites in regulating organelle function and physiological processes remains less clear. In this review we discuss the existence of a contact site between the plasma membrane (PM) and the endoplasmic reticulum (ER) in Drosophila photoreceptors. Further, we discuss the role of specific proteins present at this location in regulating phospholipid turnover and its impact in regulating a physiological process, namely phototransduction.

scholarly journals Source-sink dynamics can maintain mismatched range and bioclimatic limits even at large spatial scales

2020 ◽  
Author(s):  
Nikunj Goel ◽  
Timothy H. Keitt
Keyword(s):  
Spatial Scales ◽  
Reaction Diffusion ◽  
Dispersal Distance ◽  
Life Strategy ◽  
Stepping Stones ◽  
Reaction Diffusion Model ◽  
Primary Determinant ◽  
Source Sink ◽  
Bioclimatic Envelope

AbstractBioclimatic models assume that at broad spatial scales, climate is the primary determinant of species distribution. Meanwhile, processes such as source-sink dynamics can be ignored because they are thought to manifest at length scales comparable to species mean dispersal distance. We present a reaction-diffusion model to show species can use sink patches near the bioclimatic (or niche) limit as stepping-stones to occupy sinks much further than the mean dispersal distance, thereby extending the distribution far beyond the bioclimatic envelope. This mismatch between geographical and bioclimatic limits is mediated by the shape of the bioclimatic limit and may be significant for low growth sensitivity and fast dispersal life strategy. These findings challenge one of the core assumptions of the bioclimatic models. Therefore, we advocate that biogeographers consider the role of dispersal when using bioclimatic models to generate inferences about the ecological and evolutionary processes that determine the distribution of biota.

scholarly journals The Role of Cytoplasmic Interactions in the Collective Polarization of Tissues and its Interplay with Cellular Geometry

2018 ◽  
Author(s):  
Shahriar Shadkhoo ◽  
Madhav Mani
Keyword(s):  
Large Scale ◽  
Planar Cell Polarity ◽  
Reaction Diffusion ◽  
Directional Information ◽  
Collective Response ◽  
Reaction Diffusion Model ◽  
Necessary And Sufficient ◽  
Molecular Components ◽  
Theory And Experiments

AbstractPlanar cell polarity (PCP), the ability of a tissue to polarize coherently over multicellular length scales, provides the directional information that guides a multitude of developmental processes at cellular and tissue levels. While it is manifest that cells utilize both intra-cellular and intercellular mechanisms, how they couple together to produce the collective response remains an active area of investigation. Exploring a phenomeno-logical reaction-diffusion model, we predict a crucial, and novel, role for cytoplasmic interactions in the large-scale correlations of cell polarities. We demonstrate that finite-range (i.e. nonlocal) cytoplasmic interactions are necessary and sufficient for the robust and long-range polarization of tissues — even in the absence of global cues — and are essential to the faithful detection of weak directional signals. Strikingly, our model re-capitulates an observed influence of anisotropic tissue geometries on the orientation of polarity. In order to facilitate a conversation between theory and experiments, we compare five distinct classes of in silico mutants with experimental observations. Within this context, we propose quantitative measures that can guide the search for the participant molecular components, and the identification of their roles in the collective polarization of tissues.

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