Biochemistry (Moscow)最新文献

{"title":"Dynamics and Regulation of Cyclophilin D-Dependent Necrosis in Platelets","authors":"Artem A. Mishukov,&nbsp;Mikhail A. Panteleev,&nbsp;Anastasia N. Sveshnikova","doi":"10.1134/S0006297926601966","DOIUrl":"10.1134/S0006297926601966","url":null,"abstract":"<p>Strong physiological activation of blood platelets leads to the emergence of a non-aggregatable procoagulant subpopulation characterized by the appearance of phosphatidylserine on the outer leaflet of the plasma membrane, providing a surface for coagulation reactions. The formation of procoagulant platelets is attributed to cyclophilin D-dependent opening of the mitochondrial permeability transition pore in response to mitochondrial calcium overload; however, the mechanisms of calcium entry and subsequent necrosis have not been definitively established. We used continuous flow cytometry to analyze the main stages of this process following platelet stimulation by monitoring cytosolic calcium dynamics (Fura Red), reactive oxygen species (ROS) levels (CM-H₂DCFDA), plasma membrane integrity (calcein), mitochondrial potential [DiOC₆(3)], fluorescent fibrinogen binding, and procoagulant activity (annexin V). Receptor stimulation induced procoagulant platelet formation through an intermediate platelet subpopulation characterized by depolarized mitochondria, but polarized plasma membrane and elevated phosphatidylserine. During the early activation (less than 5 min), ROS increased sharply in the subpopulation with elevated phosphatidylserine content and steadily increased in the non-procoagulant subpopulation; by 15 min, ROS levels were comparable between the two populations. Addition of the protonophore CCCP at any point during activation did not affect the formation of procoagulant platelets. However, CCCP addition during activation of platelets preincubated with the cyclophilin D inhibitor cyclosporin A resulted in explosive necrosis. CCCP also increased calcium concentrations in resting platelets. These data help explain the contradictory effects of CCCP on platelet necrosis and highlight the importance of the voltage-dependent calcium accumulation in mitochondria. They further suggest a significance of ROS in platelet necrosis, while the loss of membrane integrity appears to be a secondary process.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 ).","pages":"1951 - 1961"},"PeriodicalIF":2.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S0006297926601966.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149230626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erebosis: An Emerging Concept of a New Type of Regulated Cell Death","authors":"Sergey V. Nikulin,&nbsp;Dmitry M. Hushpulian,&nbsp;Arpenik A. Zakharyants,&nbsp;Bobby Thomas,&nbsp;Sergey V. Kazakov,&nbsp;Irina G. Gazaryan","doi":"10.1134/S0006297926602935","DOIUrl":"10.1134/S0006297926602935","url":null,"abstract":"<p>This review briefly describes the discovery of a morphologically distinct form of regulated cell death in Drosophila, termed erebosis, which is characterized by organelle loss, nuclear flattening, and intracellular accumulation of Ance. The latter serves as a biomarker of this type of cell death but does not act as its trigger. Erebosis can be induced by amino acid deprivation accompanied by the reduced cytoplasmic viscosity, and its development is also associated with the increased heme oxygenase activity and decreased intracellular heme levels. We hypothesize that the heme-sensing protein E75 in <i>Drosophila melanogaster</i>, a homolog of mammalian REV-ERB proteins involved in circadian regulation, may provide a link between erebosis and renewal of enterocytes from the intestinal stem cells. Finally, we discuss the differences between erebosis and other forms of regulated cell death, as well as detection of ACE2 in the brains of mice in different models of Alzheimer’s disease.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 ).","pages":"1907 - 1921"},"PeriodicalIF":2.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149230641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Old Death with a New Twist: The Roles of Intrinsically Disordered Proteins and Phase Separation in Cellular Suicide","authors":"Vladimir N. Uversky","doi":"10.1134/S0006297926601656","DOIUrl":"10.1134/S0006297926601656","url":null,"abstract":"<p>Programmed cell death (PCD) is a set of tightly controlled biological pathways that eliminate obsolete or damaged cells to preserve tissue homeostasis and support development. Despite their mechanistic variations, all PCD pathways share three fundamental characteristics: a genetic basis, stringent regulation, and an active requirement for energy to drive cellular self-destruction. While PCD signaling pathways are heavily studied, their precise spatial and temporal organization remains elusive. Intrinsically disordered proteins (IDPs), liquid–liquid phase separation (LLPS), and membraneless organelles (MLOs) have emerged as fundamental principles for cellular organization, enabling rapid stress adaptation and signal integration. This review provides a brief overview of the complexity of PCD pathways and summarizes the roles of IDPs, LLPS, and MLOs in PCD regulation and execution. This biophysical perspective challenges the view of cell death as a fatalistic, binary outcome, reimagining cellular suicide not as something ‘written in stone’, but as a highly regulated continuum of decreasing vitality.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 ).","pages":"1756 - 1773"},"PeriodicalIF":2.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149230592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to: Structural and Functional Analysis of the Recombinant Aureobasidium pullulans Cutinase Variants for Efficient Polycaprolactone Degradation","authors":"Filipp K. Ermilov,&nbsp;Elena V. Eneiskaya,&nbsp;Svetlana A. Panasenko,&nbsp;Elena V. Zhurishkina,&nbsp;Kirill S. Bobrov,&nbsp;Mikhail G. Petukhov,&nbsp;Anna A. Kulminskaya,&nbsp;Irina A. Sizova","doi":"10.1134/S0006297926100019","DOIUrl":"10.1134/S0006297926100019","url":null,"abstract":"","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 ).","pages":"2082 - 2082"},"PeriodicalIF":2.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149230629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proline-Rich Peptide Complex of Calliphora vicina Larvae and Its Role in Suppressing Adaptive Bacterial Resistance","authors":"Andrey Y. Yakovlev,&nbsp;Nataliia A. Kochergina,&nbsp;Alexey G. Mittenberg","doi":"10.1134/S0006297926601346","DOIUrl":"10.1134/S0006297926601346","url":null,"abstract":"<p>Rapid rise of antibiotic resistance in Gram-negative pathogens dictates an urgent need to search for new natural factors capable of restoring efficacy of the “last-resort” drugs. In the present work, a complex of proline-rich peptides (PRPs) was isolated from the hemolymph of infected <i>Calliphora vicina</i> larvae and characterized using multistep chromatography, including reversed-phase HPLC and cation-exchange FPLC. Tandem mass spectrometry analysis revealed four peptides within the complex that exhibit structural similarity to PRPs from other dipteran species, particularly domesticin from <i>Musca domestica</i>. Although the isolated PRP complex exhibited no direct bactericidal activity against <i>Escherichia coli</i>, it effectively potentiated the effect of membrane-active peptide antibiotics, including polymyxin B. In the serial passage experiments, the PRP complex completely suppressed development of the adaptive resistance to polymyxin B in <i>E. coli.</i> The obtained data suggest that the primary function of these peptides within the co-adapted antimicrobial complexes could be inhibition of the intracellular protein synthesis and folding systems. Such mechanism likely prevents bacteria from mounting an effective stress response, thereby preventing fixation of the resistance mechanisms and ensuring evolutionary stability of the insect humoral immunity.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 ).","pages":"2013 - 2018"},"PeriodicalIF":2.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149230642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Divergence of Ribosomal Hibernation Factors in Pseudomonas putida PCL1760: Implications for Stress Adaptation and Biotechnological Applications","authors":"Aynur K. Miftakhov,&nbsp;Anastasia A. Fukalova,&nbsp;Alfred O. Onele,&nbsp;Marat M. Yusupov,&nbsp;Natalia V. Trachtmann,&nbsp;Shamil Z. Validov","doi":"10.1134/S0006297926600729","DOIUrl":"10.1134/S0006297926600729","url":null,"abstract":"<p>Ribosome hibernation is a key bacterial survival strategy under stress conditions. While most eubacteria utilize ribosome silencing factor (RsfS) and hibernation promoting factor (HPF), the functional interplay of ribosome-associated factors, including ribosome modulation factor (RMF), short HPF, and YfiA in γ-proteobacteria remains poorly understood. Here, we systematically investigated the role of these four ribosome-associated factors in <i>Pseudomonas putida</i> PCL1760 by examining their gene expression patterns, effects of overexpression, and contribution to long-term survival. Transcriptional analysis revealed that <i>rmf</i>, <i>hpf</i>, and <i>yfiA</i> are strongly induced upon entry into stationary phase with distinct temporal expression patterns, whereas <i>rsfS</i> expression remained constitutive. Overexpression of RMF, YfiA, and RsfS caused strong growth inhibition, while HPF overexpression resulted only in moderate growth suppression. Long-term survival assays of knockout mutants revealed HPF as the most critical factor, with the Δ<i>hpf</i> mutant showing a 75% loss of viability. The Δ<i>hpf</i>Δ<i>rmf</i> double mutant exhibited severely reduced survival (94% loss), whereas Δ<i>rmf</i> and Δ<i>yfiA</i> single mutants showed only moderate reduction, while the Δ<i>rsfS</i> mutant displayed no survival defects. Notably, deletion of <i>yfiA</i> against severely impaired Δ<i>hpf</i>Δ<i>rmf</i> background partially restored viability, suggesting a compensatory interaction among ribosome-associated factors. These findings reveal a synergistic relationship between HPF and RMF in long-term cellular preservation and uncover a complex regulatory network, in which distinct temporal roles of involved proteins and their cross-compensation regulate ribosome hibernation. This work advances understanding of bacterial persistence mechanisms, with potential implications for bioremediation and agricultural biotechnology.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 ).","pages":"2001 - 2012"},"PeriodicalIF":2.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149230588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sestrins as Multifunctional Regulators of Cell Viability on the Pathways from Stress to Aging","authors":"Alexander Haidurov,&nbsp;Andrei V. Budanov","doi":"10.1134/S0006297926601991","DOIUrl":"10.1134/S0006297926601991","url":null,"abstract":"<p>The interaction of cells with their environment is crucial for maintaining cellular homeostasis, and disruption of these interactions causes cellular stress and cell death. Thus, cell survival depends on the balance between proteins responsible for cell protection and those inducing cell death. Sestrins are evolutionarily conserved stress-inducible proteins that modulate cell survival under stress conditions. While prokaryotic precursors of Sestrins play a key role in protecting against oxidative stress, eukaryotic Sestrins are critically important for regulating mTORC1 and mTORC2 kinases, as well as for controlling the expression of various proteins responsible for protection against stress, mitochondrial functions, and cell death. Sestrins sustain mitochondrial activity and metabolism, activate autophagy, and limit oxidative damage, thereby promoting cell survival. Conversely, in response to DNA damage and cytokine production, Sestrins promote apoptosis by suppressing the expression of anti-apoptotic proteins, which helps prevent carcinogenesis. As modulators of cellular responses to stress, Sestrins may also serve as markers of various diseases associated with stress responses. In some tissues, expression of all Sestrin genes declines with age, which impairs the regulation of metabolism and cell death and weakens protection against age-related diseases. Thus, maintaining Sestrin activity may contribute to the prevention and treatment of various age-related diseases.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 ).","pages":"1891 - 1906"},"PeriodicalIF":2.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149230624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of Energy Metabolism in Tumor Cells by 2-DG to Overcome Drug Resistance to Doxorubicin","authors":"Nadezhda A. Persiyantseva,&nbsp;Ekaterina S. Ivanova,&nbsp;Dmitry B. Kazansky,&nbsp;Maria A. Zamkova","doi":"10.1134/S0006297926602005","DOIUrl":"10.1134/S0006297926602005","url":null,"abstract":"<p>The chemotherapeutic drug doxorubicin damages DNA of tumor cells, stopping their division. Some cells enter a metabolically active state of the therapy-induced senescence. These cells exhibit an increased dependence on glycolysis compared to untreated tumor cells, making glycolysis inhibitors potentially effective as part of combination therapy. We investigated effect of the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) on the ability of the A375, A549, and MDA-MB-231 tumor cells to overcome the senescence stage induced by a low dose of doxorubicin and resume proliferation. 2-DG inhibited accumulation of reactive oxygen species (ROS) and ATP in the senescent cells, reduced expression of mRNA of the genes encoding the glucose transporter GLUT1 and the antioxidant enzyme SOD2 and limited exit of the cells from this state but did not affect apoptosis. A reversal experiment, conducted to assess relationship between the low ATP levels in the senescent cells and their limited ability to resume proliferation, showed that addition of pyruvate together with 2-DG predictably increased the ATP production and, at the same time, number of the cells that returned to division. Our results indicate that the mechanism of action of 2-DG involves depleting ATP in the cells undergoing senescence induced by low doses of doxorubicin, preventing their exit from this stage and return to division. 2-DG could be considered as a potential chemosensitizing agent that enhances efficacy of the standard chemotherapy.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 ).","pages":"2019 - 2030"},"PeriodicalIF":2.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149230634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerated Senescence of Fibroblast-Like Cells Derived from Induced Pluripotent Stem Cells of a Patient with Wiedemann–Rautenstrauch Progeroid Syndrome","authors":"Evgeniya A. Orlova,&nbsp;Anna A. Shchukina,&nbsp;Alla I. Kalmykova","doi":"10.1134/S0006297926602819","DOIUrl":"10.1134/S0006297926602819","url":null,"abstract":"<p>The study of senescence dynamics in cells obtained from patients with accelerated aging syndromes provides a model for understanding the fundamental mechanisms of cellular senescence and for the search for approaches to slowing it down. Wiedemann–Rautenstrauch progeroid syndrome, caused by a mutation in the gene encoding the catalytic subunit of RNA polymerase III <i>POLR3A</i>, is a poorly studied syndrome with the earliest manifestation of accelerated aging features. Previously, we obtained induced pluripotent stem cells (iPSCs) from the fibroblasts of a patient with this syndrome. These iPSCs displayed changes in nucleolar structure, genome instability, and impairments in telomere maintenance mechanisms, as a result of which the telomeres did not elongate during reprogramming of the patient’s fibroblasts into iPSCs. During iPSC differentiation, we obtained fibroblast-like cells (secondary fibroblasts), which were used to study dynamics of accelerated senescence. Expression of the mutant <i>POLR3A</i> was decreased in the secondary fibroblasts compared with the iPSCs; however, features of accelerated senescence were already detectable at early passages, manifested as increased β-galactosidase activity and increased expression of the cell-cycle inhibitor p16. Differentiation was accompanied by a pronounced shortening of telomere length, which had not been restored during the reprogramming of the patient’s cells into iPSCs. The data obtained demonstrate that genomic instability of stem cells exerts an accelerating effect on the development of progeroid features during cellular differentiation.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 ).","pages":"2057 - 2070"},"PeriodicalIF":2.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149230628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria, Cell Death, and Neurodegeneration","authors":"Andrey Yu. Vinokurov,&nbsp;Artyom Yu. Baev,&nbsp;Elena V. Potapova,&nbsp;Andrey Yu. Abramov","doi":"10.1134/S0006297926601826","DOIUrl":"10.1134/S0006297926601826","url":null,"abstract":"<p>Mitochondria, acquired during the evolution of eukaryotic cells, have become essential organelles for cellular life. Beyond their well-established role in energy production, mitochondria are key regulators of intracellular signaling, acting as modulators of Ca²⁺ transport and major sources of reactive oxygen species. Mitochondrial metabolism is also closely linked to the metabolism of signaling molecules, including glutamate and monoamines. Another vital role of mitochondria is their involvement in the regulation of cell death. Disruption of mitochondrial functions contributes to the development of multiple pathological conditions, including neurodegenerative diseases. Here, we discuss how impairments in major mitochondrial processes contribute to neuronal death in neurodegenerative diseases and highlight the principal mitochondrial targets with potential pharmacological relevance.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 ).","pages":"1798 - 1821"},"PeriodicalIF":2.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149230587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}