The structure of disordered proteins presents an ensemble of different conformers, which simultaneously co-exist in solution, and dynamically transits between different conformational states separated by low energy barriers. Intrinsically disordered proteins play a central role in these processes. First, it became obvious that adaptive, fast, and reversible reprogramming of regulatory pathways in response to a stimulus is achieved with the help of the formation/disassembly of liquid-droplet compartments and, secondly, the concentration of proteins via phase separation is necessary for this mechanism. Revolutionary changes in the ideas about the organization of the intracellular space that occurred in the mid-2010s made it possible to form a unified view on the molecular mechanisms underlying cell physiology. Regardless of the type of cellular response, stress conditions cause global arrest of the gene expression and protein synthesis, inhibition of most of the "normal" signaling pathways, activation of autophagy, accumulation of a large number of unfolded, partially unfolded, misfolded proteins and RNA that have not been translated. For example, inactivation of p53 in cancer, "hijacking" of cellular stress responses by viruses to increase the rate of replication by increasing the number of chaperones, and mutation of key signal transducers such as ATF6 in UPR in neurodegenerative diseases. For many serious diseases, such as cancer, viral infection, and neurodegeneration, the association between the disease onset and the disruption of cellular stress response has been proven. For eukaryotes, the most typical pathways are the heat shock response (HSR), unfolded protein responses of the mitochondria (UPR MT), the unfolded protein responses of the endoplasmic reticulum (UPR EM), and integrated “general” stress response, which is activated by a wide range of physiological conditions, such as amino acid deficiency, viral infection, and endoplasmic reticulum stress. The adaptive response of a cell to stress is the activation of various signaling pathways that are specifically determined by the type and severity of injury. In this review, we describe the assembly of stress-induced MLOs and the stress-induced modification of existing MLOs in eukaryotes, yeasts, and prokaryotes in response to various stress factors. In addition, stress causes structural, functional, and compositional changes in the MLOs permanently present inside the cells. As a reaction to various types of stresses, stress-induced MLOs appear in the cell, enabling the preservation of the genetic and protein material during unfavourable conditions. ![]() The LLPS importance for the regulation of chemical reactions inside the cell is clearly illustrated by the reorganization of the intracellular space during stress response. IDPs play a central role in the assembly and functioning of MLOs. MLOs are multicomponent and multifunctional biological condensates, highly dynamic in structure and composition, that allow them to fine-tune the regulation of various intracellular processes. The LLPS leads to the formation of self-assembled membrane-less organelles (MLOs). This paradigm is based on the notion of the major role of liquid-liquid phase separation (LLPS) of biopolymers in the spatial-temporal organization of intracellular space. ![]() It threw the bridge from the mostly mechanistic model of the organization of the living matter to the idea of highly dynamic and functional “soft matter”. The discovery of intrinsically disordered proteins (IDPs) that do not have an ordered structure and nevertheless perform essential functions has opened a new era in the understanding of cellular compartmentalization.
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