ArticleProceedings of the National Academy of Sciences of the United States of America2024
Reconstitution of ORP-mediated lipid exchange coupled to PI4P metabolism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- The multifaceted significance of phosphoinositides in endocytic trafficking.FEBS letters · 2026Review
- Role of Oxysterol-Binding Protein Family in Cholesterol Metabolism and Cancer Progression: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Lysosomal swelling triggers LRRK2 activity.bioRxiv : the preprint server for biology · 2025Article
- Restoring metabolic flexibility: targeting organelle interaction networks in the pathogenesis and therapy of MASLD.Frontiers in cell and developmental biology · 2025Review
- Inositol metabolism as a broad-spectrum antiviral target.Frontiers in microbiology · 2025Review
- Coordination of transporter, cargo, and membrane properties during non-vesicular lipid transport.Communications biology · 2024Article
- Reconstitution of ORP-mediated lipid exchange coupled to PI4P metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
Corrections and comments
- Update of
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Oxysterol-binding protein-related proteins (ORPs) play key roles in the distribution of lipids in eukaryotic cells by exchanging sterol or phosphatidylserine for PI4P between the endoplasmic reticulum (ER) and other cell regions. However, it is unclear how their exchange capacity is coupled to PI4P metabolism. To address this question quantitatively, we analyze the activity of a representative ORP, Osh4p, in an ER/Golgi interface reconstituted with ER- and Golgi-mimetic membranes functionalized with PI4P phosphatase Sac1p and phosphatidylinositol (PI) 4-kinase, respectively. Using real-time assays, we demonstrate that upon adenosine triphosphate (ATP) addition, Osh4p creates a sterol gradient between these membranes, relying on the spatially distant synthesis and hydrolysis of PI4P, and quantify how much PI4P is needed for this process. Then, we develop a quantitatively accurate kinetic model, validated by our data, and extrapolate this to estimate to what extent PI4P metabolism can drive ORP-mediated sterol transfer in cells. Finally, we show that Sec14p can support PI4P metabolism and Osh4p activity by transferring PI between membranes. This study establishes that PI4P synthesis drives ORP-mediated lipid exchange and that ATP energy is needed to generate intermembrane lipid gradients. Furthermore, it defines to what extent ORPs can distribute lipids in the cell and reassesses the role of PI-transfer proteins in PI4P metabolism.
Indexed as
Identifiers
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.