ArticleProceedings of the National Academy of Sciences of the United States of America2020
Last step in the path of LDL cholesterol from lysosome to plasma membrane to ER is governed by phosphatidylserine.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.
- Stay in touch with the endoplasmic reticulum.Science China. Life sciences · 2024Pooled it
- StarD5 Regulates Cholesterol Homeostasis to Promote Colorectal Cancer Progression and the Cancer Stem Cell Phenotype.Molecular cancer research : MCR · 2026Article
- Small Molecules to Elevate Rab7-GTPase Activity and Lower Cholesterol Accumulation in Niemann-Pick Type C Disease.Pharmaceutical research · 2026Article
- Live-Cell Imaging and Lipidomics of Low-Density Lipoprotein Containing Intrinsically Fluorescent Cholesteryl Esters.Analytical chemistry · 2026Article
- Phosphatidylserine transporters ORP5 and ORP8 control cholesterol trafficking from the plasma membrane to the endoplasmic reticulum.Journal of lipid research · 2026Article
- Tryptophan derivatives as non-invasive diagnostic indicators for obesity-related MASLD in children and adolescents.Diabetes, obesity & metabolism · 2025Article
- Review of methods for the determination of cellular cholesterol content: principles, advantages, limitations, applications, and perspectives.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2025Review
- Metaflammation's Role in Systemic Dysfunction in Obesity: A Comprehensive Review.International journal of molecular sciences · 2025Review
- T cell cholesterol transport links intestinal immune responses to dietary lipid absorption.Science (New York, N.Y.) · 2025Article
- The multimodal transcriptional response of denervated skeletal muscle involves regulation ofProceedings of the National Academy of Sciences of the United States of America · 2025Article
- mTOR inhibition reprograms cellular lipid homeostasis by inducing alternative lipid uptake and promoting cholesterol transport.Molecular cell · 2025Article
- Protection against ferroptosis through maintaining homeostasis of docosahexaenoate-containing phospholipids.Molecular cell · 2025Article
- Quantitative modeling of rod outer segment phagocytosis and recycling.Scientific reports · 2025Article
- Sex-specific lipidomic signatures in aortic valve disease reflect differential fibro-calcific progression.Nature communications · 2025Article
- Molecular insights into human phosphatidylserine synthase 2 and its regulation of SREBP pathways.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- HDLR-SR-BI Expression and Cholesterol Uptake are Regulated via Indoleamine-2,3-dioxygenase 1 in Macrophages under Inflammation.Langmuir : the ACS journal of surfaces and colloids · 2025Article
- Proteomic and lipidomic analysis of low-density lipoprotein identifies potential biomarkers of early estrogen receptor-positive breast cancer.Cancer & metabolism · 2025Article
- Cholesterol crystals in the pathogenesis of atherosclerosis.Nature reviews. Cardiology · 2025Review
- Nonvesicular cholesterol transport in physiology.The Journal of clinical investigation · 2025Review
- Regulation of CNS Lipids by Protease Activated Receptor 1.Journal of neurochemistry · 2025Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Animal cells acquire cholesterol from receptor-mediated uptake of low-density lipoprotein (LDL), which releases cholesterol in lysosomes. The cholesterol moves to the endoplasmic reticulum (ER), where it inhibits production of LDL receptors, completing a feedback loop. Here we performed a CRISPR-Cas9 screen in human SV589 cells for genes required for LDL-derived cholesterol to reach the ER. We identified the gene encoding PTDSS1, an enzyme that synthesizes phosphatidylserine (PS), a phospholipid constituent of the inner layer of the plasma membrane (PM). In PTDSS1-deficient cells where PS is low, LDL cholesterol leaves lysosomes but fails to reach the ER, instead accumulating in the PM. The addition of PS restores cholesterol transport to the ER. We conclude that LDL cholesterol normally moves from lysosomes to the PM. When the PM cholesterol exceeds a threshold, excess cholesterol moves to the ER in a process requiring PS. In the ER, excess cholesterol acts to reduce cholesterol uptake, preventing toxic cholesterol accumulation. These studies reveal that one lipid-PS-controls the movement of another lipid-cholesterol-between cell membranes. We relate these findings to recent evidence indicating that PM-to-ER cholesterol transport is mediated by GRAMD1/Aster proteins that bind PS and cholesterol.
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Registered trials
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