ArticleProceedings of the National Academy of Sciences of the United States of America2023
Lysosome-targeted multifunctional lipid probes reveal the sterol transporter NPC1 as a sphingosine interactor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 57 citations in OpenAlex.
- Lysosomal metabolism in pancreatic cancer and its crosstalk with host physiology.Genes & development · 2026Review
- Synthesis and characterization of a novel phosphatidylinositol 5-phosphate (PI(5)P) photoaffinity probe.RSC chemical biology · 2026Article
- Bifunctional Lipid-Protein Cross-linking Efficiency and Reaction Products.Journal of the American Chemical Society · 2026Article
- Chemical biology approaches for revealing interorganelle lipid transport pathways.Current opinion in cell biology · 2026Review
- Visualizing suborganellar lipid distribution using correlative light and electron microscopy.Nature cell biology · 2026Article
- A clickable CoQ imaging probe reveals that cellular uptake and lysosomal trafficking depend on CD36 and NPC1.Redox biology · 2026Article
- Lysosome heterogeneity and diversity mapped through its distinct cellular functions.Cellular and molecular life sciences : CMLS · 2025Review
- Integrated transcriptomic analysis identifies lysosomal autophagy-related genes in sarcopenia.Scientific reports · 2025Article
- Enzyme Activity-Based Genome-wide Screening for Modifiers of Lysosomal Glucocerebrosidase Uncovers Candidate Risk Factors for Parkinson's Disease.ACS central science · 2025Article
- Article
- Trends in baseline blood lipid levels in randomized placebo-controlled trials of overweight or obesity from 1990 to 2024.World journal of diabetes · 2025Article
- Lysosomal glucocerebrosidase is needed for ciliary Hedgehog signaling: A convergent pathway contributing to Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Advances in mass spectrometry of lipids for the investigation of Niemann-pick type C disease.Lipids in health and disease · 2025Review
- Tetrandrine regulates NAADP-mediated calcium signaling through a LIMP-2-dependent and sphingosine-mediated mechanism.Nature communications · 2025Article
- Exploration of Bromodomain Proteins as Drug Targets for Niemann-Pick Type C Disease.International journal of molecular sciences · 2025Article
- The bioactive sphingolipid playbook. A primer for the uninitiated as well as sphingolipidologists.Journal of lipid research · 2025Review
- Unveiling cellular communications through rapid pan-membrane-protein labeling.Nature communications · 2025Article
- Synthetic Lipid Biology.Chemical reviews · 2025Review
- Structural and biochemical analysis of ligand binding in yeast Niemann-Pick type C1-related protein.Life science alliance · 2025Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Lysosomes are catabolic organelles involved in macromolecular digestion, and their dysfunction is associated with pathologies ranging from lysosomal storage disorders to common neurodegenerative diseases, many of which have lipid accumulation phenotypes. The mechanism of lipid efflux from lysosomes is well understood for cholesterol, while the export of other lipids, particularly sphingosine, is less well studied. To overcome this knowledge gap, we have developed functionalized sphingosine and cholesterol probes that allow us to follow their metabolism, protein interactions, and their subcellular localization. These probes feature a modified cage group for lysosomal targeting and controlled release of the active lipids with high temporal precision. An additional photocrosslinkable group allowed for the discovery of lysosomal interactors for both sphingosine and cholesterol. In this way, we found that two lysosomal cholesterol transporters, NPC1 and to a lesser extent LIMP-2/SCARB2, bind to sphingosine and showed that their absence leads to lysosomal sphingosine accumulation which hints at a sphingosine transport role of both proteins. Furthermore, artificial elevation of lysosomal sphingosine levels impaired cholesterol efflux, consistent with sphingosine and cholesterol sharing a common export mechanism.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.