Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Thermal proteome profilling in WT and CSE-/- MEF cells upon H2O2 treatment

ABSTRACT: Cellular homeostasis relies on precise regulation through chemical processes, such as protein posttranslational modifications and physical processes, such as biomolecular condensation. Aging disrupts this balance, increasing susceptibility to diseases and death. However, the mechanisms behind age-related pathogenesis remain unclear. Using chemoproteomic methods to dissect different cysteine posttranslational modifications, we found that age-related changes in cysteine redox homeostasis impact proteins ability to form biomolecular condensates. Age-related increase in sulfenylation and sulfonylation promotes phase separation and through conformational change increases proteins propensity to aggregate. Causing condensates dissolution, protein persulfidation, a protective thiol modification, prevents this. Reduced persulfidation and increased sulfonylation in aging drive abnormal phase separation, leading to shorter life and spontaneous protein aggregation in CSE-/- mice. In this study, we assessed the stability of proteins in WT and CSE-/- Mouse embryonic fibroblast mice upon H2O2 treatment.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryonic Fibroblast, Cell Culture

SUBMITTER: Thibaut Vignane

LAB HEAD: Milos Filipovic

PROVIDER: PXD045820 | Pride | 2026-05-23

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	Eclipse_02765.mzML	Mzml
	Eclipse_02765.pepXML	Pepxml
	Eclipse_02765.raw	Raw
	Eclipse_02766.mzML	Mzml
	Eclipse_02766.pepXML	Pepxml

Items per page:

1 - 5 of 8

Similar Datasets

Persulfidation and direct detection of sulfonylation in aging Brain of WT, CSE-/- and MPST-/- mice

Project description:Cellular homeostasis relies on precise regulation through chemical processes, such as protein posttranslational modifications and physical processes, such as biomolecular condensation. Aging disrupts this balance, increasing susceptibility to diseases and death. However, the mechanisms behind age-related pathogenesis remain unclear. Using chemoproteomic methods to dissect different cysteine posttranslational modifications, we found that age-related changes in cysteine redox homeostasis impact proteins ability to form biomolecular condensates. Age-related increase in sulfenylation and sulfonylation promotes phase separation and through conformational change increases proteins propensity to aggregate. Causing condensates dissolution, protein persulfidation, a protective thiol modification, prevents this. Reduced persulfidation and increased sulfonylation in aging drive abnormal phase separation, leading to shorter life and spontaneous protein aggregation in CSE-/- mice. In this study, we assessed the changes in protein persulfidation levels in brain aging. For this, we used the frontal cortex of 10 weeks, 10 months and 18 months-old WT mice . To unravel the protective role of H2S against ROS, we used the thiol-blocked samples from the persulfidation protocol to directly detect cysteine sulfonylation by mass spectrometry.

2026-05-23 | PXD045806 | Pride

Thermal proteome profilling of Ergothionine treated-cells reveals its binding to cystathionine-gamma-lyase (CSE)

Project description:Ergothioneine (ET), a dietary thione/thiol, is receiving growing attention for its possible benefits in healthy aging and metabolic resilience. Our study investigates ET's effects on healthspan in aged animals, revealing extension of lifespan and enhanced mobility in Caenorhabditis elegans, accompanied by improved stress resistance and reduced age-associated biomarkers. In aged rats, ET administration enhances exercise endurance, muscle mass, and vascularization, concomitant with higher NAD+ levels in muscle. Mechanistically, ET acts as an alternative substrate for cystathionine gamma lyase (CSE), stimulating H2S production, which increases protein persulfidation of more than 300 protein targets. Among these, protein persulfidation-driven activation of cytosolic glycerol-3-phosphate dehydrogenase (cGPDH) primarily contributes to the ET-induced NAD+ increase. ET’s effects are abolished in models lacking CSE and cGPDH, highlighting essential role of H2S signaling and protein persulfidation. These findings elucidate ET's multifaceted actions and provide insights into its therapeutic potential for combating age-related muscle decline and metabolic perturbations. To better understand the role of ET the cells, we used thermal proteome profilling of cells treated or not with ergothionine, allowing us to find new targets for the compound including CSE.

2025-01-20 | PXD051609 | Pride

Ergothioneine improves healthspan of aged animals by enhancing cGPDH activity through CSE-dependent persulfidation

2025-01-21 | PXD051587 | Pride

Eukaryotic cytoplasm is widely structured via mesoscale condensates

Project description:Compartmentalization is an essential feature of eukaryotic life and is achieved both via membrane-bound organelles, such as mitochondria, and membrane-less biomolecular condensates, such as the nucleolus. Known biomolecular condensates typically exhibit liquid-like properties and are visualized by microscopy on the scale of ~1µm. They have been studied mostly by microscopy, examining select individual proteins. So far, several dozen biomolecular condensates are known, serving a multitude of functions, for example, in the regulation of transcription, RNA processing or signalling and their malfunction can cause diseases. However, it remains unclear to what extent biomolecular condensates are utilized in cellular organization and at what length scale they typically form. Here we examine native cytoplasm from Xenopus egg extract on a global scale with quantitative proteomics, filtration, size exclusion and dilution experiments. These assays reveal that at least 18% of the proteome is organized into mesoscale biomolecular condensates at the scale of ~100nm and appear to be stabilized by RNA or gelation. We confirmed mesoscale sizes via imaging below the diffraction limit by investigating protein permeation into porous substrates with defined pore sizes. Our results show that eukaryotic cytoplasm organizes extensively via biomolecular condensates, but at surprisingly short length scales.

2023-11-02 | GSE232651 | GEO

Caenorhabditis elegans

Project description:RNA entry into biomolecular condensates

| PRJNA1283517 | ENA

pH Gradient Drives Redox Reactions in the Nucleolar Caps to Modulate Nucleolar Integrity and Function

Project description:Enzymatic catalysis has long been thought of as the primary driver of redox processes in living cells. Biomolecular condensates, formed via phase separation, exhibit unique physicochemical properties that distinguish them from the surrounding milieu. Emerging evidence indicates that the electrochemical properties of biomolecular condensates can participate in a plethora of pathophysiological processes by potentiating chemical reactions, including redox reactions. Nevertheless, the regulatory mechanisms governing the electrochemical equilibrium of biomolecular condensates and their influence on the emergent physicochemical functions, especially in cellulo, remain poorly understood. Here, we demonstrate that specific nucleolar stressors induce the formation of highly alkaline nucleolar caps, which generate an interfacial pH gradient that drives spontaneous redox reactions. Non-enzymatic reactive oxygen species (ROS) production depends on positively charged constituents within the nucleolar caps and correlates strongly with the pH microenvironment. Excessive ROS accumulation directly modulates the partition and diffusion of proteins rich in cysteine and methionine, whereas scavenging ROS markedly accelerates the recovery of nucleolar multiphase organization and functionality upon stress removal. Collectively, our findings propose a non-enzymatic redox mechanism operating within cellular condensates and highlight the critical role of physical interfaces in orchestrating the chemical dynamics of biomolecular condensates.

2026-04-25 | GSE328521 | GEO

Aberrant Phase Separation of two PKA RIbeta Neurological Disorder Mutants Leads to Mechanistically Distinct Signaling Deficits

Project description:Spatiotemporal regulation of key-node signaling molecules, such as 3’,5’-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), is critical for normal cell physiology and susceptible to dysregulation in disease. Liquid-liquid phase separation (LLPS) is broadly recognized as a fundamental component of signal regulation, yet the connections between physiological and disease-linked biomolecular condensates are not well understood. Here, we show that an understudied, brain-specific PKA regulatory subunit, RIβ, forms biomolecular condensates with distinct features from the ubiquitous isoform, RIα. We demonstrate that two RIβ mutants linked to neurodegenerative (L50R) or neurodevelopmental (R335W) pathologies produce aberrant condensates which trap the PKA catalytic subunit within a gel-like matrix or cAMP-insensitive holoenzyme complex, respectively. RIβL50R condensates, in particular, lead to disrupted spatiotemporal control of PKA signaling and diminished PKA activity, resulting in phenotypic hallmarks of neurodegeneration. Our work highlights the functional importance of biomolecular condensates and the critical link between dysregulated LLPS and neurological disorders.

2025-05-12 | GSE278676 | GEO

Phosphorylation regulates viral biomolecular condensates to promote infectious progeny production

Project description:Biomolecular condensates play important roles in diverse biological processes. Many viruses form biomolecular condensates which have been implicated in various functions critical for productive infection of host cells. The adenovirus L1-52/55 kilodalton protein (52K) was recently shown to form viral biomolecular condensates that coordinate viral genome packaging and capsid assembly. Although critical for packaging, we do not know how viral condensates are regulated during adenovirus infection. Here we show that phosphorylation of serine residues 28 and 75 within the N-terminal intrinsically disordered region of 52K modulates viral condensates in vitro and in cells, promoting liquid-like properties over condensate hardening. Furthermore, we demonstrate that phosphorylation of 52K promotes viral genome packaging and production of infectious progeny particles. Collectively, our findings provide insights into how viral condensate properties are regulated and maintained in a state conducive to their function in viral progeny production. In addition, our findings have implications for antiviral strategies aimed at targeting the regulation of viral biomolecular condensates to limit viral multiplication.

2023-12-06 | PXD046971 | Pride

CSE-induced hydorogen sulfide improves glucose homeostasis and inhibits beta-cell failure in high-fat diet mice

Project description:CSE knockout (CSE-KO)mice at age 6 months were fed a high fat diet (HFD) for 8 weeks.we determined the effects of CSE knockdown on beta-cell function and mass in islets from the mice. After 8 weeks of the HFD,blood glucose levels were drasically increaced in CSE-KO mice compared with WT mice. To assess the effect of HFD on gene expression in CSE-KO mice,we performed a comparative DNA microarray analysis 2 samples analysis.control is CSE-WT(HFD+)

2013-09-02 | E-GEOD-50458 | biostudies-arrayexpress

Pharmacologic inhibition of PCBP2 biomolecular condensates relieves Alzheimer’s disease

Project description:Biomolecular condensates are involved in a variety of neurodegenerations. These condensates are formed through phase separation mechanism. However, how they may be functional in the pathophysiology of Alzheimer’s disease (AD) remains poorly understood. Here, we report that in the brain of AD patients and animal models, an elevation of poly(C)-binding protein 2 (PCBP2) correlates with biomolecular condensation that involves phase separation. These condensates sequester large numbers of mitochondrial and mRNA-binding proteins, leading to the outside impairment of mitochondrial morphology and function, and BACE1 mRNA decay relative to amyloid deposition. We then identify a small molecule CN-0928 that inhibits the condensates by reducing PCBP2 protein level and mitigates AD pathology and cognitive decline, in which CN-0928 binding to a target protein integrator complex subunit 1 (INTS1) allows to regulate PCBP2 expression. Our findings place PCBP2 condensates as a key player that cooperates the seemingly disparate but important pathways, and show pharmacological modulation of PCBP2 as an effective approach for treating AD.

2025-09-30 | GSE306042 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data