Label-Free Techniques for Probing Biomolecular Condensates DOI
Khalid A. Ibrahim,

Akhil S. Naidu,

Helena Miljkovic

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(16), P. 10738 - 10757

Published: April 12, 2024

Biomolecular condensates play important roles in a wide array of fundamental biological processes, such as cellular compartmentalization, regulation, and other biochemical reactions. Since their discovery first observations, an extensive expansive library tools has been developed to investigate various aspects properties, encompassing structural compositional information, material evolution throughout the life cycle from formation eventual dissolution. This Review presents overview expanded set methods that researchers use probe properties biomolecular across diverse scales length, concentration, stiffness, time. In particular, we review recent years' exciting development label-free techniques methodologies. We broadly organize into 3 categories: (1) imaging-based techniques, transmitted-light microscopy (TLM) Brillouin (BM), (2) force spectroscopy atomic (AFM) optical tweezer (OT), (3) microfluidic platforms emerging technologies. point out tools' key opportunities, challenges, future perspectives analyze correlative potential well compatibility with techniques. Additionally, namely, differential dynamic (DDM) interferometric scattering (iSCAT), have huge for applications studying condensates. Finally, highlight how some these can be translated diagnostics therapy purposes. hope this serves useful guide new field aids advancing biophysical study

Language: Английский

Targeting ROS in cancer: rationale and strategies DOI
Christophe Glorieux, Shihua Liu, Dunyaporn Trachootham

et al.

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(8), P. 583 - 606

Published: July 9, 2024

Language: Английский

Citations

149

Stress-related biomolecular condensates in plants DOI Creative Commons
Jorge Solís-Miranda, Monika Chodasiewicz, Aleksandra Skirycz

et al.

The Plant Cell, Journal Year: 2023, Volume and Issue: 35(9), P. 3187 - 3204

Published: May 10, 2023

Biomolecular condensates are membraneless organelle-like structures that can concentrate molecules and often form through liquid-liquid phase separation. condensate assembly is tightly regulated by developmental environmental cues. Although research on biomolecular has intensified in the past 10 years, our current understanding of molecular mechanisms components underlying their formation remains its infancy, especially plants. However, recent studies have shown may be central to plant acclimation stress conditions. Here, we describe mechanism, regulation, properties stress-related plants, focusing granules processing bodies, 2 most well-characterized condensates. In this regard, showcase proteomes bodies an attempt suggest methods for elucidating composition function Finally, discuss how modulate responses they might used as targets biotechnological efforts improve tolerance.

Language: Английский

Citations

48

Misfolded protein oligomers: mechanisms of formation, cytotoxic effects, and pharmacological approaches against protein misfolding diseases DOI Creative Commons
Dillon J. Rinauro, Fabrizio Chiti, Michele Vendruscolo

et al.

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: Feb. 20, 2024

The conversion of native peptides and proteins into amyloid aggregates is a hallmark over 50 human disorders, including Alzheimer's Parkinson's diseases. Increasing evidence implicates misfolded protein oligomers produced during the formation process as primary cytotoxic agents in many these devastating conditions. In this review, we analyze processes by which are formed, their structures, physicochemical properties, population dynamics, mechanisms cytotoxicity. We then focus on drug discovery strategies that target ability to disrupt cell physiology trigger degenerative processes.

Language: Английский

Citations

47

Small-molecule properties define partitioning into biomolecular condensates DOI Creative Commons
Sabareesan Ambadi Thody, Hanna D. Clements, Hamid Baniasadi

et al.

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(11), P. 1794 - 1802

Published: Sept. 13, 2024

Language: Английский

Citations

40

The E3 ubiquitin ligase MARCH2 protects against myocardial ischemia-reperfusion injury through inhibiting pyroptosis via negative regulation of PGAM5/MAVS/NLRP3 axis DOI Creative Commons

Shuolin Liu,

Yaguang Bi,

Tianting Han

et al.

Cell Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Feb. 27, 2024

Inflammasome activation and pyroptotic cell death are known to contribute the pathogenesis of cardiovascular diseases, such as myocardial ischemia-reperfusion (I/R) injury, although underlying regulatory mechanisms remain poorly understood. Here we report that expression levels E3 ubiquitin ligase membrane-associated RING finger protein 2 (MARCH2) were elevated in ischemic human hearts or mouse upon I/R injury. Genetic ablation MARCH2 aggravated infarction cardiac dysfunction Single-cell RNA-seq analysis suggested loss prompted NLRP3 inflammasome cardiomyocytes. Mechanistically, phosphoglycerate mutase 5 (PGAM5) was found act a novel regulator MAVS-NLRP3 signaling by forming liquid-liquid phase separation condensates with MAVS fostering recruitment NLRP3. directly interacts PGAM5 promote its K48-linked polyubiquitination proteasomal degradation, resulting reduced PGAM5-MAVS co-condensation, consequently inhibition cardiomyocyte pyroptosis. AAV-based re-introduction significantly ameliorated I/R-induced heart dysfunction. Altogether, our findings reveal mechanism where MARCH2-mediated ubiquitination negatively regulates PGAM5/MAVS/NLRP3 axis protect against pyroptosis

Language: Английский

Citations

34

Micronuclei and Cancer DOI
Melody Di Bona,

Samuel F. Bakhoum

Cancer Discovery, Journal Year: 2024, Volume and Issue: 14(2), P. 214 - 226

Published: Jan. 10, 2024

Chromosome-containing micronuclei are a feature of human cancer. Micronuclei arise from chromosome mis-segregation and characterize tumors with elevated rates chromosomal instability. Although their association cancer has been long recognized, only recently have we broadened our understanding the mechanisms that govern formation role in tumor progression. In this review, provide brief historical account micronuclei, depict underpinning creation, illuminate capacity to propel evolution through genetic, epigenetic, transcriptional transformations. We also posit prospect leveraging as biomarkers therapeutic targets chromosomally unstable cancers. cells serve pivotal catalysts for progression, instigating transformative genomic, alterations. This comprehensive review not synthesizes present comprehension but outlines framework translating knowledge into pioneering therapeutics, thereby illuminating novel paths personalized management.

Language: Английский

Citations

33

Transcriptional condensates: a blessing or a curse for gene regulation? DOI Creative Commons

Martín Stortz,

Diego M. Presman, Valeria Levi

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Feb. 16, 2024

Whether phase-separation is involved in the organization of transcriptional machinery and if it aids or inhibits process a matter intense debate. In this Mini Review, we will cover current knowledge regarding role condensates on gene expression regulation. We summarize latest discoveries relationship between condensate formation, genome organization, activity, focusing strengths weaknesses experimental approaches used to interrogate these aspects transcription living cells. Finally, discuss challenges for future research.

Language: Английский

Citations

27

Biomolecular Condensates in Contact with Membranes DOI
Agustín Mangiarotti, Rumiana Dimova

Annual Review of Biophysics, Journal Year: 2024, Volume and Issue: 53(1), P. 319 - 341

Published: Feb. 16, 2024

Biomolecular condensates are highly versatile membraneless organelles involved in a plethora of cellular processes. Recent years have witnessed growing evidence the interaction these droplets with membrane-bound structures. Condensates' adhesion to membranes can cause their mutual molding and regulation, is fundamental relevance intracellular organization communication, organelle remodeling, embryogenesis, phagocytosis. In this article, we review advances understanding membrane-condensate interactions, focus on vitro models. These minimal systems allow precise characterization tuning material properties both provide workbench for visualizing resulting morphologies quantifying interactions. interactions give rise diverse biologically relevant phenomena, such as molecular-level restructuring membrane, nano- microscale ruffling condensate-membrane interface, coupling protein lipid phases.

Language: Английский

Citations

26

Protein misfolding and amyloid nucleation through liquid–liquid phase separation DOI
S. Mukherjee, Manisha Poudyal, K. Dave

et al.

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(10), P. 4976 - 5013

Published: Jan. 1, 2024

Protein misfolding and amyloid aggregation, linked to neurodegenerative diseases, can result from liquid–liquid phase separation (LLPS) a subsequent liquid-to-solid transition. This represents LLPS as generic mechanism in nucleation.

Language: Английский

Citations

25

Structure is beauty, but not always truth DOI Creative Commons
James S. Fraser, Mark A. Murcko

Cell, Journal Year: 2024, Volume and Issue: 187(3), P. 517 - 520

Published: Feb. 1, 2024

Language: Английский

Citations

21