ArticleProceedings of the National Academy of Sciences of the United States of America2017
mTORC1 activates SREBP-2 by suppressing cholesterol trafficking to lysosomes in mammalian cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 2 of them syntheses that pooled it.
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Who cites it
86 citing papers in PubMed, 2 syntheses or guidelines pooled it, 136 citations in OpenAlex.
- Cholesterol homeostasis and cancer: a new perspective on the low-density lipoprotein receptor.Cellular oncology (Dordrecht, Netherlands) · 2022Pooled it
- Identification of CXCR4 Upregulation in Diffuse Large B-Cell Lymphoma Associated with Prognostic Significance and Clinicopathological Characteristics.Disease markers · 2022Pooled it
- Circulating factors induced by time-restricted eating drive metabolic reprogramming in endothelial cells.GeroScience · 2026Article
- Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism.Nature metabolism · 2026Article
- The interplay between lipid metabolism, cancer progression and anti-cancer immunity.Experimental & molecular medicine · 2026Review
- [Mechanism ofNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Lipid Metabolic Rewiring During Continuous Prostate Cancer Progression Defines a Biologically Relevant Four-Gene Prognostic Signature.Biological procedures online · 2026Article
- Lipopolysaccharide stimulates dynamic changes in B cell metabolism to promote proliferation.eLife · 2026Article
- The Contribution of Cholesterol and Squalene Synthase in Cancer: Molecular Mechanisms, Lipid Rafts and Therapeutic Approaches.Medicinal research reviews · 2026Review
- HIF-2α induction in de novo lipogenesis in metabolic dysfunction-associated steatohepatitis is dependent on IL-21 signaling.The Journal of biological chemistry · 2026Article
- Dysregulated lipid metabolism and hypomyelination in postnatal peroxisome-deficientFrontiers in molecular neuroscience · 2026Article
- Cholesterol metabolism and cancer: Molecular mechanisms, immune regulation and an epidemiological perspective (Review).International journal of molecular medicine · 2025Review
- SPNS1 variants cause multiorgan disease and implicate lysophospholipid transport as critical for mTOR-regulated lipid homeostasis.The Journal of clinical investigation · 2025Article
- Oxidized Low-Density Lipoprotein as a Potential Target for Enhancing Immune Checkpoint Inhibitor Therapy in Microsatellite-Stable Colorectal Cancer.Antioxidants (Basel, Switzerland) · 2025Review
- ABCG8‑mediated sterol efflux increases cancer cell progression via the LRP6/Wnt/β‑catenin signaling pathway in radiotherapy‑resistant MDA‑MB‑231 triple‑negative breast cancer cells.International journal of molecular medicine · 2025Article
- Hypercapnia Increases Influenza A Virus Infection of Bronchial Epithelial Cells by Augmenting Cellular Cholesterol via mTOR and Akt.International journal of molecular sciences · 2025Article
- CYP51A1 drives resistance to pH-dependent cell death in pancreatic cancer.Nature communications · 2025Article
- SLC13A2 promotes hepatocyte metabolic remodeling and liver regeneration by enhancing de novo cholesterol biosynthesis.The EMBO journal · 2025Article
- An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma.The Journal of clinical investigation · 2025Article
- Lysosome-Mitochondrial Crosstalk in Cellular Stress and Disease.Antioxidants (Basel, Switzerland) · 2025Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
mTORC1 is known to activate sterol regulatory element-binding proteins (SREBPs) including SREBP-2, a master regulator of cholesterol synthesis. Through incompletely understood mechanisms, activated mTORC1 triggers translocation of SREBP-2, an endoplasmic reticulum (ER) resident protein, to the Golgi where SREBP-2 is cleaved to translocate to the nucleus and activate gene expression for cholesterol synthesis. Low ER cholesterol is a well-established trigger for SREBP-2 activation. We thus investigated whether mTORC1 activates SREBP-2 by reducing cholesterol delivery to the ER. We report here that mTORC1 activation is accompanied by low ER cholesterol and an increase of SREBP-2 activation. Conversely, a decrease in mTORC1 activity coincides with a rise in ER cholesterol and a decrease in SERBP-2 activity. This rise in ER cholesterol is of lysosomal origin: blocking the exit of cholesterol from lysosomes by U18666A or NPC1 siRNA prevents ER cholesterol from increasing and, consequently, SREBP-2 is activated without mTORC1 activation. Furthermore, when mTORC1 activity is low, cholesterol is delivered to lysosomes through two membrane trafficking pathways: autophagy and rerouting of endosomes to lysosomes. Indeed, with dual blockade of both pathways by Atg5
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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.