Reorganization of Cell Compartmentalization Induced by Stress

Abstract

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. 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". 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. The LLPS leads to the formation of self-assembled membrane-less organelles (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. IDPs play a central role in the assembly and functioning of MLOs. 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. 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. In addition, stress causes structural, functional, and compositional changes in the MLOs permanently present inside the cells. 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.

Per Aspera ad Chaos: Vladimir Uversky’s Odyssey through the Strange World of Intrinsically Disordered Proteins

“…Phase separation-Liquid-liquid phase separation (LLPS) represents one of the major functional areas in which IDPs are involved and has been attracting a lot of interest in the scientific community in recent years. This is also evident from the numbers of contributions on this topic received in our SI, with five scientific articles and three reviews [9][10][11][12][13][14][15][16] regarding both computational prediction and biochemical analysis of condensation propensity.…”

Sequence Sensitivity in Membrane Remodeling by Polyampholyte Condensates

“…Liquid–liquid phase separation (LLPS) is a phenomenon that has been widely studied in recent years due to its importance in various biological processes. − Intrinsically disordered proteins (IDPs) and nucleic acids have emerged as key regulators of LLPS in biological systems, due to the presence of multivalent interactions. − LLPS is related to intracellular compartmentalization through the formation of membraneless organelles (e.g., nucleoli, P-bodies, stress granules, Cajal bodies, etc.) that support various cellular functions including stress response, protein degradation, signal transduction and are therefore also implicated in diseases. − In the past decade, there has been a growing interest in understanding the formation, structure, and dynamics of such macromolecular condensates in the bulk phase, both theoretically and experimentally. − …”

Nucleolar- and Nuclear-Stress-Induced Membrane-Less Organelles: A Proteome Analysis through the Prism of Liquid–Liquid Phase Separation

“…In this work, we analyzed the propensity for spontaneous phase separation of the proteomes of two MLOs formed in the nucleus in response to stress, which have a partially overlapping composition, but a different functional activity and morphology: A-bodies (amyloid bodies) and nuclear stress bodies [ 12 , 13 ].…”