ArticleScience advances2023
An SPNS1-dependent lysosomal lipid transport pathway that enables cell survival under choline limitation.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 46 citations in OpenAlex.
- Robust analytical methods for bis(monoacylglycero)phosphate profiling in health and disease.Nature protocols · 2026Review
- LPLAT7 reutilizes unsaturated 1-lysophospholipids formed during lysosomal phospholipid degradation.Journal of lipid research · 2026Article
- Zebrafish screen of schizophrenia risk genes reveals convergent dysregulation of cholesterol metabolism.bioRxiv : the preprint server for biology · 2026Article
- Lysosomal Immunoprecipitation (LysoIP) from Cells and Tissues for Metabolomic and Proteomic Analyses.Methods in molecular biology (Clifton, N.J.) · 2026Article
- SPNS1 is an essential cellular factor for EV-A71 by acting as a transporter of viral pocket factor.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Enzyme Activity-Based Genome-wide Screening for Modifiers of Lysosomal Glucocerebrosidase Uncovers Candidate Risk Factors for Parkinson's Disease.ACS central science · 2025Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- SPNS1 variants cause multiorgan disease and implicate lysophospholipid transport as critical for mTOR-regulated lipid homeostasis.The Journal of clinical investigation · 2025Article
- Technologies for Decoding Cancer Metabolism with Spatial Resolution.Cold Spring Harbor perspectives in medicine · 2025Review
- Article
- Review
- Molecular basis of Spns1-mediated lysophospholipid transport from the lysosome.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cellular and organismal function of choline metabolism.Nature metabolism · 2025Review
- Spns1-dependent endocardial lysosomal function drives valve morphogenesis through Notch1-signaling.iScience · 2024Article
- Spns1 is an iron transporter essential for megalin-dependent endocytosis.American journal of physiology. Renal physiology · 2024Article
- Gaucher disease provides a unique window into Parkinson disease pathogenesis.Nature reviews. Neurology · 2024Review
- CNS-wide repopulation by hematopoietic-derived microglia-like cells corrects progranulin deficiency in mice.Nature communications · 2024Article
- Glycerophosphodiesters inhibit lysosomal phospholipid catabolism in Batten disease.Molecular cell · 2024Article
- Lack of SPNS1 results in accumulation of lysolipids and lysosomal storage disease in mouse models.JCI insight · 2024Article
- Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology.Nature reviews. Molecular cell biology · 2024Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Lysosomes degrade macromolecules and recycle their nutrient content to support cell function and survival. However, the machineries involved in lysosomal recycling of many nutrients remain to be discovered, with a notable example being choline, an essential metabolite liberated via lipid degradation. Here, we engineered metabolic dependency on lysosome-derived choline in pancreatic cancer cells to perform an endolysosome-focused CRISPR-Cas9 screen for genes mediating lysosomal choline recycling. We identified the orphan lysosomal transmembrane protein SPNS1 as critical for cell survival under choline limitation. SPNS1 loss leads to intralysosomal accumulation of lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE). Mechanistically, we reveal that SPNS1 is a proton gradient-dependent transporter of LPC species from the lysosome for their re-esterification into phosphatidylcholine in the cytosol. Last, we establish that LPC efflux by SPNS1 is required for cell survival under choline limitation. Collectively, our work defines a lysosomal phospholipid salvage pathway that is essential under nutrient limitation and, more broadly, provides a robust platform to deorphan lysosomal gene function.
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What OpenQuestion holds
Registered trials
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.