


Vol 42, No 3 (2025)
Articles
Optimizing oxygenic photosynthesis: pH-regulation of electron transport in chloroplasts in silico
Abstract
In this work, we carried out mathematical modeling of the electron and proton transport regulation in the thylakoid membranes of chloroplasts under different operating conditions of the electron transport chain (ETC) of chloroplasts. The study is based on the kinetic model of the functioning of the chloroplasts ETC proposed by us earlier, which describes the redox transformations of the reaction center of photosystem 1 (PS1), ferredoxin molecules, several forms of plastoquinone (PS2-related molecules PQA, PQB, and the pool of plastoquinones PQ/PQH2), as well as plastocyanin molecules. The model also simulates the induction curve of chlorophyll a fluorescence in the leaves of higher plants adapted to darkness. The multiphase kinetic curves obtained by varying the model parameters reflecting the rate of functioning of the Calvin–Benson cycle and the cyclic electron transport path around PS1 are in reasonable agreement with the published experimental data. The main result of our work is that it mathematically describes how pH-dependent regulatory processes occurring in various parts of the chloroplast ETC (non-cyclic, cyclic, and pseudocyclic electron transport) affect the kinetics of induction processes (slow induction of fluorescence and redox transformations of the PS1 photoreaction center) in dark-adapted chloroplasts of plants.



Formation of pores in membranes asymmetrical in lipid composition of monolayers
Abstract
Plasma membranes perform a barrier function in cells, preventing free exchange between the external environment and the intracellular space. The permeability of the plasma cell membrane can be artificially increased by forming through pores. The outer and inner monolayers of the plasma membranes of cells typically have different lipid composition. Currently, a theoretical description of the poration of membranes with monolayers symmetrical in lipid composition has been developed. In the present work, we consider the process of pore formation in membranes, whose monolayers have different spontaneous curvatures due to the difference in their lipid composition. In the framework of the theory of lipid membrane elasticity and considering hydrophobic interactions, the dependence of the pore energy on the radius is calculated. It is shown that the dependences of pore energy on radius are qualitatively different in asymmetric and symmetrical membranes. The pore energy in the asymmetric membrane differs from the pore energy in the symmetric membrane at any values of the spontaneous curvature of the monolayers of the symmetric membrane. Thus, it is incorrect to predict the course of the pore formation in an asymmetric membrane on the basis of data obtained on symmetric membranes; the asymmetry of lipid composition (spontaneous curvature) of monolayers should be explicitly taken into account.



MKT-077 suppresses the functional activity of isolated mouse skeletal muscle mitochondria
Abstract
This study demonstrates the effect of the rhodocyanine derivative MKT-077 on the function of isolated mitochondria from mouse skeletal muscle. MKT-077 was shown to dose-dependently inhibit mitochondrial respiration fueled by glutamate/malate (complex I substrates) or succinate (complex II substrate). This effect of MKT-077 was accompanied by a decrease in the membrane potential of organelles and was associated with both inhibition of the activity of complexes I and II of the mitochondrial respiratory chain and an increase in the proton permeability of the inner mitochondrial membrane. Molecular docking revealed sites in mitochondrial respiratory chain complex I that have an affinity for MKT-077 comparable to that of the specific inhibitor rotenone. At a concentration of 5 μM, MKT-077 caused a significant increase in hydrogen peroxide production by skeletal muscle mitochondria. However, 1 μM MKT-077 reduced the pro-oxidant effect of antimycin A. In addition, MKT-077 dose-dependently reduced the ability of mitochondria to uptake and retain calcium ions in the matrix. The article discusses the mechanisms of possible action of MKT-077 on the functioning of skeletal muscle mitochondria and their contribution to the side effects observed during the therapy of pathological conditions in vivo using this rhodocyanine derivative.



In silico evaluation of the effect of geometrical configuration and charge of opioid antagonists on their binding to opioid receptors
Abstract
The effect of the geometric configuration and charge of molecules of opioid receptor (OR) agonists and antagonists on binding to mu-, delta-, and kappa-opioid receptors was studied using the molecular docking method. For the docking procedure, we used the three-dimensional structures of the ligands obtained by X-ray diffraction analysis and available in the Cambridge Crystallographic Data Centre (CCDC), as well as their three-dimensional models built in a molecular editor. The three-dimensional crystal structure of nalmefene, which is absent from the CCDC database, was obtained for the first time in the presented study by X-ray diffraction analysis. Protonated and deprotonated forms of the ligands were tested. The results of the study using the example of morphine, codeine, naloxone, naltrexone, and nalmefene showed that the method of obtaining three-dimensional geometric structures of OR ligands has no effect on the calculated values of the free energy of binding ΔG, which indicates the possibility of using ligand models constructed in silico in computational experiments. The protonation state of the ligand molecule, on the contrary, has a significant effect on the free energy of binding to OR, which can affect the properties of this group of drugs when pH values in the body change. When considering the peculiarities of binding of opioid enantiomers into the ligand-binding center of mu-opioid receptors using the example of morphine, it was shown that (–)-morphine and (+)-morphine share a common site for the cationic group, and not for the phenolic hydroxyl, as was previously assumed. At the same time, studies have shown that molecular docking only partially allows describing the pharmacological action of analgesics and their antagonists. For some substances, such as codeine and synthetic (+)-morphine, in silico experiments there was an overestimation of the effectiveness of the interaction of the drug with the OR, which requires continued improvement of the corresponding calculation methods and models.



Effect of cadmium ions on the content of ∆5-sterols in microdomains of the vacuolar membrane
Abstract
The effect of 100 μM cadmium ions (Cd2+) on the content of ∆5-sterols in microdomains of the vacuolar membrane was studied. Cd2+ was shown to cause an increase in the content of sterols in the tonoplast microdomains of zone 2 of the sucrose gradient and a decrease in the sterol content in zone 4. The sum of free sterols was higher than the sum of sterol esters in both the tonoplast and microdomains of zones 2, 4, and 6. The composition of free sterols in microdomains was dominated by β-sitosterol, and in the tonoplast by stigmasterol. The composition of sterol esters in the tonoplast also showed a high content of stigmasterol and a high content of β-sitosterol and campesterol in zone 2 microdomains. Compared with controls not exposed to Cd2+, changes in the % content of ∆5-sterols were observed. The changes affected mainly sterols involved in the structural organization of the lipid bilayer. These results suggest that sterols of tonoplast microdomains may participate in the cell response to Cd2+.



Specific and non-specific changes in plasmalemma lipid content induced by different types of abiotic stress
Abstract
Effects of different abiotic stresses (hyperosmotic, hypoosmotic, and oxidative) on the lipid profile of the plasma membrane of table beet root cells (Beta vulgaris L.) were studied. Changes in the composition of membrane lipids under different types of stress had their distinctive features. The content of such lipids as phosphatidylethanolamines, phosphatidylglycerols, monogalactosyldiacylglycerides (MGDG), pentodecanoic fatty acid, cholesterol and stigmasterol, decreased under all types of stress, while the content of digalactosyldiacylglycerides (DGDG), arachic fatty acid and β-sitosterol and the DGDG/MGDG ratio increased under all types of stress. These effects of stress can be classified as nonspecific. However, for some lipids, stress-induced changes in their content depended on the type of stress. For example, the content of sphingolipids increased significantly under hyperosmotic stress and decreased under hypoosmotic and oxidative stress. In contrast, the content of sterols increased under hypoosmotic stress and decreased under hyperosmotic stress, and the content of sterol esters increased only under oxidative stress. Changes in the composition of these lipids can be regarded as specific. Changes in the content of phosphatidic acid, phosphatidylserines, phosphatidylinositols, phosphatidylcholines, and most fatty acids, as well as in ratio of phosphatidylcholines to phosphatidylethanolamines and some other parameters can also be attributed to specific. In conclusion, this study demonstrates that different types of abiotic stress induce different changes in membrane lipid content. These results may contribute to a better understanding of adaptation mechanisms and help in the development of new strategies to improve plant stress resistance.



КРАТКИЕ СООБЩЕНИЯ
Molecular cloning and heterologous expression of GPR120 from the mouse taste tissue
Abstract
The existence of fat taste along with the generally recognized taste modalities (sweet, bitter, umami, salty, and sour) is currently a subject of scientific debate and active research. Available data on the signaling cascade triggered by long-chain fatty acids (FAs) in the taste cell indicate its similarity to the transduction of sweet, bitter, and umami stimuli, but the initial stages of transduction of fatty stimuli remain unclear. A member of the G-protein-coupled receptor superfamily, GPR120, is considered as one of the candidates for the role of a long-chain FA receptor operating in the taste bud. At the same time, available reports implicating GPR120 in the FA perception by the peripheral taste system are highly contradictory. In order to create a platform for further study of the contribution of GPR120 to FA transduction, we cloned GPR120 from the mouse taste tissue and expressed it in HEK-293 cells. In contrast to the parental HEK-293 cells, GPR120-positive HEK-293 cells generated receptor-like Ca2+ transients in response to long-chain FA application, thus confirming the literature data on the coupling of the GPR120 receptor to the phosphoinositide cascade and intracellular Ca2+ mobilization. The HEK-293 cells expressing recombinant GPR120 receptor may present a useful cell model for screening natural and synthetic ligands of this receptor and analyzing its coupling to intracellular signaling pathways. Co-expression of GPR120 with other signaling proteins involved in the transduction of fatty stimuli in taste cells may be useful for interpreting taste cell responses to FAs.


