Oxidative Cysteine Post Translational Modifications Drive the Redox Code Underlying Neurodegeneration and Amyotrophic Lateral Sclerosis DOI Creative Commons

Anna Percio,

Michela Cicchinelli, Domiziana Masci

и другие.

Antioxidants, Год журнала: 2024, Номер 13(8), С. 883 - 883

Опубликована: Июль 23, 2024

Redox dysregulation, an imbalance between oxidants and antioxidants, is crucial in the pathogenesis of various neurodegenerative diseases. Within this context, "redoxome" encompasses network redox molecules collaborating to maintain cellular balance signaling. Among these, cysteine-sensitive proteins are fundamental for homeostasis. Due their reactive thiol groups, cysteine (Cys) residues particularly susceptible oxidative post-translational modifications (PTMs) induced by free radicals (reactive oxygen, nitrogen, sulfur species) which profoundly affect protein functions. Cys-PTMs, forming what referred as "cysteinet" proteome, essential signaling both physiological pathological conditions, including neurodegeneration. Such significantly influence misfolding aggregation, key hallmarks diseases such Alzheimer's, Parkinson's, notably, amyotrophic lateral sclerosis (ALS). This review aims explore complex landscape PTMs environment, elucidating impact on neurodegeneration at level. By investigating specific regulatory networks involved, particular emphasis placed link dysregulation ALS, highlighting pathology a prime example disease wherein distinct hallmark.

Язык: Английский

ROS-dependent S-palmitoylation activates cleaved and intact gasdermin D DOI
Gang Du, Liam B. Healy, Liron David

и другие.

Nature, Год журнала: 2024, Номер 630(8016), С. 437 - 446

Опубликована: Апрель 10, 2024

Язык: Английский

Процитировано

83
Phase separation of p62: roles and regulations in autophagy DOI
Xue Huang,

Jinpei Zhang,

Jia Yao

и другие.

Trends in Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

1
Altered Protein Palmitoylation as Disease Mechanism in Neurodegenerative Disorders DOI
Jakub Włodarczyk, Raja Bhattacharyya, Kim Doré

и другие.

Journal of Neuroscience, Год журнала: 2024, Номер 44(40), С. e1225242024 - e1225242024

Опубликована: Окт. 2, 2024

Palmitoylation, a lipid-based posttranslational protein modification, plays crucial role in regulating various aspects of neuronal function through altering membrane-targeting, stabilities, and protein–protein interaction profiles. Disruption palmitoylation has recently garnered attention as disease mechanism neurodegeneration. Many proteins implicated neurodegenerative diseases associated dysfunction, including but not limited to amyloid precursor protein, β-secretase (BACE1), postsynaptic density 95, Fyn, synaptotagmin-11, mutant huntingtin, superoxide dismutase 1, undergo palmitoylation, recent evidence suggests that altered contributes the pathological characteristics these disruption cellular processes. In addition, dysfunction enzymes catalyze depalmitoylation been connected development neurological disorders. This review highlights some latest advances our understanding regulation explores potential therapeutic implications.

Язык: Английский

Процитировано

5
Temporal and protein-specific S-palmitoylation supports synaptic and neural network plasticity DOI Creative Commons

Agata Pyty,

Rabia Ijaz,

Anna Buszka

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

Abstract S-palmitoylation, a dynamic post-translational modification, has long been suggested to play pivotal role in synaptic plasticity, learning, and memory. However, its precise impact on proteins function remains unclear. In this study, we show that acute protein depalmitoylation the hippocampus differentially affects short- long-term depending synapse type. Strikingly, also reprograms neuronal spiking timing following associative network activation. Our research identifies pre- postsynaptic dynamically regulated by S-palmitoylation during plasticity suggests modification occurs isolated excitatory synapses. We demonstrate targets specific within minutes is not proteome-wide. These findings mark significant advance understanding how lipid modifications drive neural adaptability, memory, learning.

Язык: Английский

Процитировано

0
Perturbation of de novo lipogenesis hinders MERS-CoV assembly and release, but not the biogenesis of viral replication organelles DOI Creative Commons
Maria Soultsioti, Anja W. M. de Jong,

N. Blomberg

и другие.

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

ABSTRACT Coronaviruses hijack host cell metabolic pathways and resources to support their replication. They induce extensive endomembrane remodeling generate viral replication organelles exploit membranes for assembly budding of enveloped progeny virions. Because the overall significance membranes, we sought gain insight into role factors involved in lipid metabolism cells infected with Middle East respiratory syndrome coronavirus (MERS-CoV). We employed a single-cycle infection approach combination pharmacological inhibitors, biochemical assays, lipidomics, light electron microscopy. Pharmacological inhibition acetyl-CoA carboxylase (ACC) fatty acid synthase (FASN), key de novo biosynthesis, led pronounced MERS-CoV particle release. Inhibition ACC profound switch Huh7 cells, altering lipidomic profile inducing lipolysis. However, despite changes induced by inhibitor, biogenesis remained unaffected. Instead, appeared affect trafficking post-translational modifications envelope proteins. Electron microscopy revealed an accumulation nucleocapsids early stages, indicating that is adversely impacted inhibition. Notably, palmitoylation resulted similar effects, while supplementation exogenous palmitic reversed compound’s inhibitory possibly reflecting crucial need spike proteins virus assembly. IMPORTANCE (MERS-CoV) etiological agent zoonotic disease limited transmissibility between humans. still considered high-priority pathogen closely monitored WHO due its high lethality rate around 35% laboratory-confirmed infections. Like other positive-strand RNA viruses, relies on cell’s endomembranes various stages cycle. spite this general reliance metabolism, mechanistic insights are very limited. In our study, show (ACC), enzyme biosynthesis pathway, significantly disrupts without exerting negative effect organelles. Furthermore, study highlights potential as target development host-directed antiviral therapeutics against coronaviruses.

Язык: Английский

Процитировано

0
ZDHHC9 mediates SMURF2 palmitoylation to promote lipid synthesis DOI Creative Commons
Wenting Dai,

Bin Xue,

Yuan Yuan

и другие.

Cell investigation., Год журнала: 2025, Номер 1(2), С. 100015 - 100015

Опубликована: Апрель 10, 2025

Язык: Английский

Процитировано

0
Cycling Molecular Assemblies for Selective Cancer Cell Golgi Disruption DOI Open Access
Weiyi Tan, Qiuxin Zhang, Zhiyu Liu

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 5, 2025

The Golgi apparatus is a critical organelle responsible for intracellular trafficking and signaling, orchestrating essential processes such as protein lipid sorting

Язык: Английский

Процитировано

0
A facile assay for zDHHC palmitoyl transferase activation elucidates effects of mutation and modification DOI Creative Commons
Naoko Adachi,

Douglas T. Hess,

Takehiko Ueyama

и другие.

Journal of Lipid Research, Год журнала: 2025, Номер unknown, С. 100743 - 100743

Опубликована: Янв. 1, 2025

At least 10% of proteins constituting the human proteome are subject to S-acylation by a long-chain fatty acid, thioesterified Cys thiol side chain. Fatty (prototypically, S-palmitoylation) operates across eukaryotic phylogeny and cell type. S-palmitoylation is carried out in mammalian cells family 23-24 dedicated zDHHC palmitoyl transferase enzymes, mutation zDHHCs associated with number pathophysiologies. Activation auto-S-palmitoylation, transthioesterification active site acyl-CoA, necessary first step zDHHC-mediated protein S-palmitoylation. Most prior vitro assessments activation have utilized purified zDHHCs, time- effort-intensive approach, which removes from their native membrane environment. We describe here facile assay for membranes. overexpressed HA-tagged wild-type or mutant cultured HEK293 prepared whole fraction, was incubated fluorescent CoA (NBD-palmitoyl-CoA) followed SDS-PAGE, fluorescence imaging western blotting HA. show mutational analysis that, as assayed, auto-S-palmitoylation NBD-palmitoyl-CoA limited Cys. Application revealed differential effects on posttranslational modification, mutations disease, particular cancer. Our provides means assessing thus differentiating post-translational modification versus secondary functionality resulting altered interaction substrate palmitoyl-proteins.

Язык: Английский

Процитировано

0
Cell Labeling with 15-YNE Is Useful for Tracking Protein Palmitoylation and Metabolic Lipid Flux in the Same Sample DOI Creative Commons

Nadine Merz,

Karin Schilling,

Dominique Thomas

и другие.

Molecules, Год журнала: 2025, Номер 30(2), С. 377 - 377

Опубликована: Янв. 17, 2025

Protein S-palmitoylation is the process by which a palmitoyl fatty acid attached to cysteine residue of protein via thioester bond. A range methodologies are available for detection S-palmitoylation. In this study, two methods different proteins were compared after metabolic labeling cells with 15-hexadecynoic (15-YNE) ascertain their relative usefulness. It was hypothesized that traceable lipid would affect metabolism and cellular lipidome. we developed method track 15-YNE incorporation into lipids using liquid chromatography high-resolution mass spectrometry (LC-HRMS) as well palmitoylation in same sample. We observed time- concentration-dependent calnexin succinate dehydrogenase complex flavoprotein subunit (SDHA) depending on cell type. The clickable fluorophore or biotin azide followed immunoprecipitation shown be equally useful. incorporated wide array classes during process, yet it did not appear modify overall composition cells. conclusion, show useful tracer detect both

Язык: Английский

Процитировано

0
Greasing the wheels of inflammasome formation: regulation of NLRP3 function by S-linked fatty acids DOI Creative Commons
Daniel M. Williams, Andrew A. Peden

Biochemical Society Transactions, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

NLRP3 is an inflammasome seeding pattern recognition receptor that initiates a pro-inflammatory signalling cascade in response to changes intracellular homeostasis are indicative of bacterial infection or tissue damage. Several types post-translational modification (PTM) have been identified added regulate its activity. Recent progress has revealed subject further type PTM, S-acylation (or palmitoylation), which involves the reversible addition long-chain fatty acids target cysteine residues by opposing sets enzymes. This review provides overview recent studies as important modifier function. The essential role recruitment membranes and consequences S-acylation-dependent membrane on localisation activation discussed detail.

Язык: Английский

Процитировано

0