Golgi-IP, a tool for multimodal analysis of Golgi molecular content

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(20)

Published: May 8, 2023

The Golgi is a membrane-bound organelle that essential for protein and lipid biosynthesis. It represents central trafficking hub sorts proteins lipids to various destinations or secretion from the cell. has emerged as docking platform cellular signaling pathways including LRRK2 kinase whose deregulation leads Parkinson disease. dysfunction associated with broad spectrum of diseases cancer, neurodegeneration, cardiovascular diseases. To allow study at high resolution, we report rapid immunoprecipitation technique (Golgi-IP) isolate intact mini-stacks subsequent analysis their content. By fusing Golgi-resident TMEM115 three tandem HA epitopes (GolgiTAG), purified using Golgi-IP minimal contamination other compartments. We then established an pipeline liquid chromatography coupled mass spectrometry characterize human proteome, metabolome, lipidome. Subcellular proteomics confirmed known identified not previously Golgi. Metabolite profiling metabolome revealed enrichment uridine-diphosphate (UDP) sugars derivatives, which consistent roles in glycosylation. Furthermore, targeted metabolomics validated SLC35A2 subcellular transporter UDP-hexose. Finally, lipidomics showed phospholipids phosphatidylcholine, phosphatidylinositol, phosphatidylserine are most abundant glycosphingolipids enriched this compartment. Altogether, our work establishes comprehensive molecular map provides powerful method precision health

Language: Английский

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An SPNS1-dependent lysosomal lipid transport pathway that enables cell survival under choline limitation

Science Advances, Journal Year: 2023, Volume and Issue: 9(16)

Published: April 19, 2023

Lysosomes degrade macromolecules and recycle their nutrient content to support cell function survival. However, the machineries involved in lysosomal recycling of many nutrients remain be discovered, with a notable example being choline, an essential metabolite liberated via lipid degradation. Here, we engineered metabolic dependency on lysosome-derived choline pancreatic cancer cells perform endolysosome-focused CRISPR-Cas9 screen for genes mediating recycling. We identified orphan transmembrane protein SPNS1 as critical survival under limitation. loss leads intralysosomal accumulation lysophosphatidylcholine (LPC) lysophosphatidylethanolamine (LPE). Mechanistically, reveal that is proton gradient–dependent transporter LPC species from lysosome re-esterification into phosphatidylcholine cytosol. Last, establish efflux by required Collectively, our work defines phospholipid salvage pathway limitation and, more broadly, provides robust platform deorphan gene function.

Language: Английский

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Investigating Past, Present, and Future Trends on Interface Between Marine and Medical Research and Development: A Bibliometric Review

Marine Drugs, Journal Year: 2025, Volume and Issue: 23(1), P. 34 - 34

Published: Jan. 10, 2025

The convergence of marine sciences and medical studies has the potential for substantial advances in healthcare. This study uses bibliometric topic modeling to map progression research themes from 2000 2023, with an emphasis on interdisciplinary subject sciences. Building global publication output at interface between using Hierarchical Dirichlet Process, we discovered dominating topics during three periods, emphasizing shifts focus development trends. Our data show a significant rise output, indicating growing interest bioresources applications. paper identifies two main areas active research, "natural product biochemistry" "trace substance genetics", both great therapeutic potential. We used social network analysis collaborative networks identify prominent scholars institutions driving this progress. indicates important paths policy R&D management operating crossroads healthcare innovation It also underscores significance quantitative foresight methods teams identifying interpreting future scientific convergences breakthroughs.

Language: Английский

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An organism-level quantitative flux model of energy metabolism in mice

Cell Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Harnessing Immune Cell Metabolism to Modulate Alloresponse in Transplantation

Transplant International, Journal Year: 2024, Volume and Issue: 37

Published: March 19, 2024

Immune cell metabolism plays a pivotal role in shaping and modulating immune responses. The metabolic state of cells influences their development, activation, differentiation, overall function, impacting both innate adaptive immunity. While glycolysis is crucial for activation effector function CD8 T cells, regulatory mainly use oxidative phosphorylation fatty acid oxidation, highlighting how different programs shape cells. Modification may provide new therapeutic approaches to prevent rejection avoid immunosuppressive toxicities. In particular, the distinct patterns suppressive subsets offer promising opportunities target pathways that influence responses graft outcomes. Herein, we review main used by techniques available assay metabolism, evidence supporting possibility shifting response towards tolerogenic profile modifying energetic metabolism.

Language: Английский

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Recent advances of microbial metabolism analysis: from metabolic molecules to environments

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(11), P. 2941 - 2950

Published: Sept. 18, 2023

Language: Английский

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Identification of high sugar diet-induced dysregulated metabolic pathways in muscle using tissue-specific metabolic models in Drosophila

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 28, 2024

Individual tissues perform highly specialized metabolic functions to maintain whole-body homeostasis. Although Drosophila serves as a powerful model for studying human diseases, lack of tissue-specific models makes it challenging quantitatively assess the processes individual and disease in this organism. To address issue, we reconstructed 32 genome-scale (GEMs) using pseudo-bulk single cell transcriptomics data, revealing distinct network structures across tissues. Leveraging enzyme kinetics flux analyses, predicted tissue-dependent pathway activities, recapitulating known tissue identifying signatures, supported by metabolite profiling. Moreover, demonstrate utility GEMs context, examined effect high sugar diet (HSD) on muscle metabolism. Together with 13C-glucose isotopic tracer studies, identified glyceraldehyde 3-phosphate dehydrogenase (GAPDH) rate-limiting glycolysis response HSD. Decreased GAPDH activity was linked increased NADH/NAD+ ratio oxidation GAPDH. Furthermore, introduced index predict validate additionally perturbed pathways, including fructose butanoate Altogether, our results represent significant advance generating quantitative analyses Drosophila, highlighting their use dysregulated pathways model.

Language: Английский

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Dual stable isotopes enhance lipidomic studies in bacterial model organism Enterococcus faecalis

Analytical and Bioanalytical Chemistry, Journal Year: 2023, Volume and Issue: 415(17), P. 3593 - 3605

Published: May 19, 2023

Language: Английский

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Oncogenic metabolic rewiring independent of proliferative control in human mammary epithelial cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: April 8, 2022

Summary The use of isotopic tracers and metabolic flux analysis (MFA) has unveiled a number pathways differentially activated in cancer cells. To support efforts to design effective therapies for cancer, we sought distinguish behavior versus normal cells growing at the same rate. this end, performed 13 C-isotope tracing MFA human mammary epithelial (HMECs) harboring different combinations oncogenes. By introducing new quantity termed intensity, defined as pathway divided by specific growth rate, showed that metabolism is dually controlled proliferation oncogenotypes. C-MFA further revealed oxidative pentose phosphate (oxPPP), malate dehydrogenase (MDH) isocitrate (IDH) were most enhanced cancerous HMECs. Drug targeting these selectively reduced tumorigenic HMEC line. Our study provides direct evidence than proliferating

Language: Английский

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Graphene quantum dots disturbed the energy homeostasis by influencing lipid metabolism of macrophages

Toxicology, Journal Year: 2022, Volume and Issue: 484, P. 153389 - 153389

Published: Dec. 5, 2022

Language: Английский

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