Cold Spring Harbor Perspectives in Medicine, Год журнала: 2023, Номер 13(12), С. a041420 - a041420
Опубликована: Дек. 1, 2023
Yetis Gultekin1, Matthew G. Vander Heiden1,2 and Evan C. Lien3 1Koch Institute for Integrative Cancer Research, Massachusetts of Technology, Cambridge, 02139, USA 2Department Medicine, Dana-Farber Institute, Boston, 02115, 3Department Metabolism Nutritional Programming, Van Andel Grand Rapids, Michigan 49503, Correspondence: mvh{at}mit.edu
Язык: Английский
Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(20)
Опубликована: Май 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
Язык: Английский
Процитировано
38
Science Advances, Год журнала: 2023, Номер 9(16)
Опубликована: Апрель 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.
Язык: Английский
Процитировано
36
Marine Drugs, Год журнала: 2025, Номер 23(1), С. 34 - 34
Опубликована: Янв. 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.
Язык: Английский
Процитировано
1
Cell Metabolism, Год журнала: 2025, Номер unknown
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0
Transplant International, Год журнала: 2024, Номер 37
Опубликована: Март 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.
Язык: Английский
Процитировано
3
Science China Chemistry, Год журнала: 2023, Номер 66(11), С. 2941 - 2950
Опубликована: Сен. 18, 2023
Язык: Английский
Процитировано
7
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Апрель 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.
Язык: Английский
Процитировано
2
Analytical and Bioanalytical Chemistry, Год журнала: 2023, Номер 415(17), С. 3593 - 3605
Опубликована: Май 19, 2023
Язык: Английский
Процитировано
5
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown
Опубликована: Апрель 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
Язык: Английский
Процитировано
8
Toxicology, Год журнала: 2022, Номер 484, С. 153389 - 153389
Опубликована: Дек. 5, 2022
Язык: Английский
Процитировано
8