ArticleeLife2019
Intracellular cholesterol trafficking is dependent upon NPC2 interaction with lysobisphosphatidic acid.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 73 citations in OpenAlex.
- Codon-optimizedMolecular therapy. Nucleic acids · 2026Article
- Dietary Rosmarinic Acid Improved the Growth, Immunity and Antioxidation ofAnimals : an open access journal from MDPI · 2026Article
- Single-cell transcriptomics identifies a p21-activated kinase important for survival of the zoonotic parasiteiScience · 2026Article
- SARS-CoV-2 ORF3a blocks lysosomal cholesterol egress by disrupting VPS39-regulated NPC2 trafficking and BMP metabolism.Cell reports · 2026Article
- Noncanonical PI(4,5)PScience advances · 2026Article
- Transport of sphingolipids by yeast Npc2 supports phase separation of the vacuole membrane.The Journal of biological chemistry · 2026Article
- Discovery of Autophagy Modulators that Increase I1061T NPC1 Expression and Promote Cholesterol Efflux in Niemann-Pick Type C Patient-Derived Fibroblasts.ACS chemical biology · 2026Article
- Mechanistic Basis of Cholesterol Binding and Transfer in NPC2: Insights From Molecular Dynamics Simulations.Chembiochem : a European journal of chemical biology · 2026Article
- Lysosomal homeostasis at the crossroads of neurodegeneration.The Journal of clinical investigation · 2026Review
- Unveiling Lipid Dysregulation: Lipidomics of Mouse Brain and Isolated Myelin in Niemann-Pick Disease Type C1.bioRxiv : the preprint server for biology · 2026Article
- Review
- Fighting fire with fire: PLA2G15 inhibition mobilizes BMP lipids to combat NPC1 disease.Metabolism open · 2025Article
- Lysosome heterogeneity and diversity mapped through its distinct cellular functions.Cellular and molecular life sciences : CMLS · 2025Review
- SARS-CoV-2 ORF3a blocks lysosomal cholesterol egress by disrupting VPS39-regulated NPC2 trafficking and BMP metabolism.bioRxiv : the preprint server for biology · 2025Article
- Soma to neuron communication links stress adaptation to stress avoidance behavior.bioRxiv : the preprint server for biology · 2025Article
- An Integrated Platform for High-Throughput Extraction and Mass Spectrometry-Based Quantification of Cholesterol and Sphingosine.Analytical chemistry · 2025Article
- Article
- Structural and biochemical analysis of ligand binding in yeast Niemann-Pick type C1-related protein.Life science alliance · 2025Article
- Molecular determinants of phospholipid treatment to reduce intracellular cholesterol accumulation in NPC1 deficiency.The Journal of biological chemistry · 2024Article
- Two-pore channels regulate endomembrane tension to enable remodeling and resolution of phagolysosomes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Unesterified cholesterol accumulation in the late endosomal/lysosomal (LE/LY) compartment is the cellular hallmark of Niemann-Pick C (NPC) disease, caused by defects in the genes encoding NPC1 or NPC2. We previously reported the dramatic stimulation of NPC2 cholesterol transport rates to and from model membranes by the LE/LY phospholipid lysobisphosphatidic acid (LBPA). It had been previously shown that enrichment of NPC1-deficient cells with LBPA results in cholesterol clearance. Here we demonstrate that LBPA enrichment in human NPC2-deficient cells, either directly or via its biosynthetic precursor phosphtidylglycerol (PG), is entirely ineffective, indicating an obligate functional interaction between NPC2 and LBPA in cholesterol trafficking. We further demonstrate that NPC2 interacts directly with LBPA and identify the NPC2 hydrophobic knob domain as the site of interaction. Together these studies reveal a heretofore unknown step of intracellular cholesterol trafficking which is critically dependent upon the interaction of LBPA with functional NPC2 protein.
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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.