PML-Bodies as Open Dynamic System

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According to modern concepts, the formation of functional dynamic structures in a cell that do not have a membrane (membrane-less organelles) is based on reversible phase transitions of the “liquid - liquid” type of biopolymers. The properties of such systems significantly depend on the changes in external conditions and the action of various stimuli. One of the best studied membrane-less organelles are PML bodies. These polyfunctional protein organelles are present in most cell types and are involved in the regulation of transcription, cell differentiation, stress response, etc. It is known that all PML are involved in the formation of PML bodies. PML bodies are sensors of the cell stress response to an increase in reactive oxygen species. Therefore, it can be assumed that such stressful conditions will cause significant changes in the structure and properties of PML bodies. We examined the effect of acute oxidative stress caused by cells treatment with hydrogen peroxide (H2O2) on the localization, morphology, and dynamics of the exchange of isoforms of the scaffold PML protein of these structures with nucleoplasm. Stressful conditions led to a significant decrease in the proportion of the mobile fraction during the restoration of fluorescence after photobleaching of the fusion proteins EGFP-PML-I, EGFP-PML-II, and EGFP-PML-V involved in PML bodies. At the same time cells treatmened with H2O2 does not change the dynamics of the exchange of isoforms EGFP-PML-III, EGFP-PML-IV, EGFP-PML-VI with nucleoplasm. Thus, oxidative stress causes a redistribution of scaffold proteins within PML bodies. The obtained data proved the dynamic nature of membrane-less organelles as an open dynamic systems existing at the edge of chaos, whose evolution essentially depends on the changes in external conditions. This work was supported by the Russian Science Foundation (RSF No 19-15-00107) and the RF President Fellowship SP-259.2019.4.