Publications by authors named "Semen V Nesterov"

4 Publications

  • Page 1 of 1

Liquid-liquid phase separation as a common organizing principle of intracellular space and biomembranes providing dynamic adaptive responses.

Biochim Biophys Acta Mol Cell Res 2021 Oct 20;1868(11):119102. Epub 2021 Jul 20.

Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Institutskiy pereulok, 9, Dolgoprudny 141700, Russia; Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC07, Tampa, FL 33612, USA. Electronic address:

This work is devoted to the phenomenon of liquid-liquid phase separation (LLPS), which has come to be recognized as fundamental organizing principle of living cells. We distinguish separation processes with different dimensions. Well-known 3D-condensation occurs in aqueous solution and leads to membraneless organelle (MLOs) formation. 2D-films may be formed near membrane surfaces and lateral phase separation (membrane rafts) occurs within the membranes themselves. LLPS may also occur on 1D structures like DNA and the cyto- and nucleoskeleton. Phase separation provides efficient transport and sorting of proteins and metabolites, accelerates the assembly of metabolic and signaling complexes, and mediates stress responses. In this work, we propose a model in which the processes of polymerization (1D structures), phase separation in membranes (2D structures), and LLPS in the volume (3D structures) influence each other. Disordered proteins and whole condensates may provide membrane raft separation or polymerization of specific proteins. On the other hand, 1D and 2D structures with special composition or embedded IDRs can nucleate condensates. We hypothesized that environmental change may trigger a LLPS which can propagate within the cell interior moving along the cytoskeleton or as an autowave. New phase propagation quickly and using a low amount of energy adjusts cell signaling and metabolic systems to new demands. Cumulatively, the interconnected phase separation phenomena in different dimensions represent a previously unexplored system of intracellular communication and regulation which cannot be ignored when considering both physiological and pathological cell processes.
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http://dx.doi.org/10.1016/j.bbamcr.2021.119102DOI Listing
October 2021

On the Role of Normal Aging Processes in the Onset and Pathogenesis of Diseases Associated with the Abnormal Accumulation of Protein Aggregates.

Biochemistry (Mosc) 2021 Mar;86(3):275-289

Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, 141701, Russia.

Aging is a prime systemic cause of various age-related diseases, in particular, proteinopathies. In fact, most diseases associated with protein misfolding are sporadic, and their incidence increases with aging. This review examines the process of protein aggregate formation, the toxicity of such aggregates, the organization of cellular systems involved in proteostasis, and the impact of protein aggregates on important cellular processes leading to proteinopathies. We also analyze how manifestations of aging (mitochondrial dysfunction, dysfunction of signaling systems, changes in the genome and epigenome) facilitate pathogenesis of various proteinopathies either directly, by increasing the propensity of key proteins for aggregation, or indirectly, through dysregulation of stress responses. Such analysis might help in outlining approaches for treating proteinopathies and extending healthy longevity.
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http://dx.doi.org/10.1134/S0006297921030056DOI Listing
March 2021

NMDA and GABA receptor presence in rat heart mitochondria.

Chem Biol Interact 2018 Aug 6;291:40-46. Epub 2018 Jun 6.

Institute of Cytochemistry and Molecular Pharmacology, 6-th Radialnaya str. 24-14, Moscow, 115404, Russia. Electronic address:

The purpose of this study is to demonstrate the presence of three more receptors in mitochondria. Two N-methyl-d-aspartate receptor (NMDAR) subunits (NR1 and NR2B) are found by protein immunoblot and immunogold labeling in mitochondria fraction isolated from rat heart. These data allow supposing NMDAR presence and functioning in the inner mitochondrial membrane. There are no signs of receptor presence obtained in heart tissue lysate, that indicates the receptor localization exactly in mitochondria. The possible receptor functions discussed are its participation in calcium transport and in excitation-metabolism coupling. Besides, preliminary evidence is obtained of GABA and GABA receptors presence in heart mitochondria. One can surmise their role in metabolism regulation and their possible co-operation with NMDAR just as in the nervous system.
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http://dx.doi.org/10.1016/j.cbi.2018.06.004DOI Listing
August 2018

On the regulative role of the glutamate receptor in mitochondria.

Biol Chem 2016 May;397(5):445-58

The purpose of this work was to study the regulative role of the glutamate receptor found earlier in the brain mitochondria. In the present work a glutamate-dependent signaling system with similar features was detected in mitochondria of the heart. The glutamate-dependent signaling system in the heart mitochondria was shown to be suppressed by γ-aminobutyric acid (GABA). The GABA receptor presence in the heart mitochondria was shown by golding with the use of antibodies to α- and β-subunits of the receptor. The activity of glutamate receptor was assessed according to the rate of synthesis of hydrogen peroxide. The glutamate receptor in mitochondria could be activated only under conditions of hypoxic stress, which in model experiments was imitated by blocking Complex I by rotenone or fatty acids. The glutamate signal in mitochondria was shown to be calcium- and potential-dependent and the activation of the glutamate cascade was shown to be accompanied by production of hydrogen peroxide. It was discovered that H2O2 synthesis involves two complexes of the mitochondrial electron transfer system - succinate dehydrogenase (SDH) and fatty acid dehydrogenase (ETF:QO). Thus, functions of the glutamate signaling system are associated with the system of respiration-glycolysis switching (the Pasteur-Crabtree) under conditions of hypoxia.
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http://dx.doi.org/10.1515/hsz-2015-0289DOI Listing
May 2016
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