ArticleNature cell biology2019
ER-lysosome contacts enable cholesterol sensing by mTORC1 and drive aberrant growth signalling in Niemann-Pick type C.
Article in Nature cell biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 2 of them syntheses that pooled it.
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Who cites it
189 citing papers in PubMed, 2 syntheses or guidelines pooled it, 304 citations in OpenAlex.
- Stay in touch with the endoplasmic reticulum.Science China. Life sciences · 2024Pooled it
- Inter-organellar Communication in Parkinson's and Alzheimer's Disease: Looking Beyond Endoplasmic Reticulum-Mitochondria Contact Sites.Frontiers in neuroscience · 2022Pooled it
- mTORC1-TFEB/TFE3 signaling is associated with bile acid diversification during hepatic metabolic adaptation.Science advances · 2026Article
- Cholesterol maintains the degradative capacity of lysosomes during clearance and recycling of dysfunctional mitochondria.Nature communications · 2026Article
- Inter-Organelle Membrane Contact Sites as Physiological Regulatory Hubs in the Brain: From Neurons to Glial Cells.Biomolecules · 2026Review
- Lipid-gated vesicular trafficking directs HSPA1A to the plasma membrane through the endo-lysosomal network.Cell stress & chaperones · 2026Article
- Lactate-mediated cholesterol uptake promotes liver cancer progression via the SCARB1-autophagy axis.EMBO reports · 2026Article
- Lysosome-derived methylated arginine is a signalling metabolite controlling the lipidome.Nature cell biology · 2026Article
- NPC2 Regulates Glioblastoma Cholesterol Metabolism and Malignant Behavior via GPX4-Linked Ferroptosis.Cell biology international · 2026Article
- Article
- HKDC1 contributes to aberrant lysosome-mitochondria contact in Niemann-Pick disease type C.bioRxiv : the preprint server for biology · 2026Article
- Mapping brain cell-type-specific diversity of lysosomal proteins.Cell research · 2026Article
- Noncanonical PI(4,5)PScience advances · 2026Article
- Genetic variants in Rps4x cause intellectual disability with dysmorphic features, microcephaly, and autism.NPJ genomic medicine · 2026Article
- Targeting the ferritinophagy-lysosome axis as a therapeutic vulnerability in gastroenteropancreatic neuroendocrine tumors.Cell reports. Medicine · 2026Article
- Lysosomal phosphoinositide turnover acts upstream of RagGTPase-mTORC1 and controls muscle growth.Nature metabolism · 2026Article
- E3 ligase AREL1 controls perinuclear localization of lysosomes and supports Purkinje cell survival.The EMBO journal · 2026Article
- A Supramolecular Nanoscavengers: Based "Cargo-Exchange" Breaking Cholesterol Metabolic Dysregulation for Glioblastoma Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Selective DHCR24 Blocker SH42 Inhibits ACE2 Binding and Cellular Entry of SARS-CoV-2 Spike Proteins More Efficiently Than Atorvastatin.Research (Washington, D.C.) · 2026Article
- VAPB is a negative regulator of STING-mediated innate immune signaling.Science advances · 2025Article
129 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Cholesterol activates the master growth regulator, mTORC1 kinase, by promoting its recruitment to the surface of lysosomes by the Rag guanosine triphosphatases (GTPases). The mechanisms that regulate lysosomal cholesterol content to enable mTORC1 signalling are unknown. Here, we show that oxysterol binding protein (OSBP) and its anchors at the endoplasmic reticulum (ER), VAPA and VAPB, deliver cholesterol across ER-lysosome contacts to activate mTORC1. In cells lacking OSBP, but not other VAP-interacting cholesterol carriers, the recruitment of mTORC1 by the Rag GTPases is inhibited owing to impaired transport of cholesterol to lysosomes. By contrast, OSBP-mediated cholesterol trafficking drives constitutive mTORC1 activation in a disease model caused by the loss of the lysosomal cholesterol transporter, Niemann-Pick C1 (NPC1). Chemical and genetic inactivation of OSBP suppresses aberrant mTORC1 signalling and restores autophagic function in cellular models of Niemann-Pick type C (NPC). Thus, ER-lysosome contacts are signalling hubs that enable cholesterol sensing by mTORC1, and targeting the sterol-transfer activity of these signalling hubs could be beneficial in patients with NPC.
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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.