Reversible protein aggregation as cytoprotective mechanism against heat stress

Gallardo, Paola; Salas-Pino, Silvia; Daga, Rafael R.

doi:10.1007/s00294-021-01191-2

Cited by 14 publications

(13 citation statements)

References 80 publications

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“…The intracellular liquid–liquid phase separation (LLPS) of proteins and RNA leading to the formation of membraneless organelles (MLOs) is now established as a fundamental process in cell biology, exhibiting functions in cellular signaling, , transcriptional and translational regulation, enzymatic activity, and stress response. , In fact, MLOs formed during stress conditions are part of a more complex orchestrated cellular feedback that also encompasses the formation of reversible protein aggregates and filaments, all serving to increase fitness and survival. ,, Stress granules (SGs) are one of such type of cytoprotective assemblies, formed in response to heat stress (HS), that among under functions are known to recruit and transiently store misfolded proteins. ,− …”

Section: Introductionmentioning

confidence: 99%

“…HS leads to local or global unfolding of proteins, resulting in the exposure of hydrophobic segments that were otherwise buried in native conditions . The protein quality control (PQC) machinery (chaperones, ubiquitin-proteasome, or autophagy), engages with such unfolded/misfolded states, refolding, shielding, or degrading them, thus precluding toxic aggregation. ,− These actions are usually rationalized with partition models, where clients can directly bind to PQC as monomers, oligomers, or aggregates, with all these states being further sequestered by SGs and thus optimizing client clearance. ,,− Nevertheless, mutations or failure in the PQC promoted by cellular stress or aging leads to deleterious changes in the material properties of the SG components, triggering pathological phase transitions. ,− …”

Section: Introductionmentioning

confidence: 99%

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Sequestration of Proteins in Stress Granules Relies on the In-Cell but Not the In Vitro Folding Stability

et al. 2021

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Stress granules (SGs) are among the most studied membraneless organelles that form upon heat stress (HS) to sequester unfolded, misfolded, or aggregated protein, supporting protein quality control (PQC) clearance. The folding states that are primarily associated with SGs, as well as the function of the phase separated environment in adjusting the energy landscapes, remain unknown. Here, we investigate the association of superoxide dismutase 1 (SOD1) proteins with different folding stabilities and aggregation propensities with condensates in cells, in vitro and by simulation. We find that irrespective of aggregation the folding stability determines the association of SOD1 with SGs in cells. In vitro and in silico experiments however suggest that the increased flexibility of the unfolded state constitutes only a minor driving force to associate with the dynamic biomolecular network of the condensate. Specific protein–protein interactions in the cytoplasm in comparison to SGs determine the partitioning of folding states between the respective phases during HS.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sequestration of Proteins in Stress Granules Relies on the In-Cell but Not the In Vitro Folding Stability

et al. 2021

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“…Small heat shock proteins (sHsps) and disaggregase machineries ensure that the aggregation is reversible despite the stable nature of protein aggregates [please see ( Gallardo et al, 2021 ) for further details]. sHsps are regarded as first line of defense when cells experience proteotoxic stress by interacting with a wide plethora of substrates, forming stable sHsp-substrate complexes leading to their sequestration.…”

Section: Similarities and Differences Of Biomolecular Condensates And...mentioning

confidence: 99%

Reversible protein assemblies in the proteostasis network in health and disease

Kohler

Andréasson

2023

Front. Mol. Biosci.

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While proteins populating their native conformations constitute the functional entities of cells, protein aggregates are traditionally associated with cellular dysfunction, stress and disease. During recent years, it has become clear that large aggregate-like protein condensates formed via liquid-liquid phase separation age into more solid aggregate-like particles that harbor misfolded proteins and are decorated by protein quality control factors. The constituent proteins of the condensates/aggregates are disentangled by protein disaggregation systems mainly based on Hsp70 and AAA ATPase Hsp100 chaperones prior to their handover to refolding and degradation systems. Here, we discuss the functional roles that condensate formation/aggregation and disaggregation play in protein quality control to maintain proteostasis and why it matters for understanding health and disease.

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“…Another example constitutes the “intra-nuclear quality-control compartment” located in the nucleus of S. cerevisiae upon heat stress. This nuclear structure, located close to the nucleolus, contains misfolded cytosolic and nuclear proteins ( Figure 2 ; Kaganovich et al, 2008 ; reviewed by Gallardo et al, 2021 ).…”

Section: Nuclear Granules and Bodies Under Stressmentioning

confidence: 99%

Nuclear dynamics: Formation of bodies and trafficking in plant nuclei

Muñoz-Díaz

Sáez‐Vasquez

2022

Front. Plant Sci.

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The existence of the nucleus distinguishes prokaryotes and eukaryotes. Apart from containing most of the genetic material, the nucleus possesses several nuclear bodies composed of protein and RNA molecules. The nucleus is separated from the cytoplasm by a double membrane, regulating the trafficking of molecules in- and outwards. Here, we investigate the composition and function of the different plant nuclear bodies and molecular clues involved in nuclear trafficking. The behavior of the nucleolus, Cajal bodies, dicing bodies, nuclear speckles, cyclophilin-containing bodies, photobodies and DNA damage foci is analyzed in response to different abiotic stresses. Furthermore, we research the literature to collect the different protein localization signals that rule nucleocytoplasmic trafficking. These signals include the different types of nuclear localization signals (NLSs) for nuclear import, and the nuclear export signals (NESs) for nuclear export. In contrast to these unidirectional-movement signals, the existence of nucleocytoplasmic shuttling signals (NSSs) allows bidirectional movement through the nuclear envelope. Likewise, nucleolar signals are also described, which mainly include the nucleolar localization signals (NoLSs) controlling nucleolar import. In contrast, few examples of nucleolar export signals, called nucleoplasmic localization signals (NpLSs) or nucleolar export signals (NoESs), have been reported. The existence of consensus sequences for these localization signals led to the generation of prediction tools, allowing the detection of these signals from an amino acid sequence. Additionally, the effect of high temperatures as well as different post-translational modifications in nuclear and nucleolar import and export is discussed.

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Reversible protein aggregation as cytoprotective mechanism against heat stress

Cited by 14 publications

References 80 publications

Sequestration of Proteins in Stress Granules Relies on the In-Cell but Not the In Vitro Folding Stability

Sequestration of Proteins in Stress Granules Relies on the In-Cell but Not the In Vitro Folding Stability

Reversible protein assemblies in the proteostasis network in health and disease

Nuclear dynamics: Formation of bodies and trafficking in plant nuclei

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