ArticleProceedings of the National Academy of Sciences of the United States of America2015
ORMDL orosomucoid-like proteins are degraded by free-cholesterol-loading-induced autophagy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Intersection of Sphingolipid and Sterol Metabolism at the Level of Orm Proteins in Yeast.Cells · 2026Article
- ORMDL Proteins Turnover via Proteasome and Autophagy Is Cell-Type Dependent and Tied to Ceramide Homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- ORM1 Mediates Ln-IgG-Induced Podocyte Damage and Autophagy via the AMPK/mTOR Signaling.Organogenesis · 2025Article
- Intricate Regulation of Sphingolipid Biosynthesis: An In-Depth Look Into ORMDL-Mediated Regulation of Serine Palmitoyltransferase.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Advances in ORMDL Research in Malignant Tumors: A Review.OncoTargets and therapy · 2025Review
- Sphingolipid-Induced Bone Regulation and Its Emerging Role in Dysfunction Due to Disease and Infection.International journal of molecular sciences · 2024Review
- Three kingdoms and one ceramide to rule them all. A comparison of the structural basis of ceramide-dependent regulation of sphingolipid biosynthesis in animals, plants, and fungi.Advances in biological regulation · 2024Article
- Simultaneous reduction of all ORMDL proteins decreases the threshold of mast cell activation.Scientific reports · 2023Article
- ORMDL in metabolic health and disease.Pharmacology & therapeutics · 2023Review
- Crosstalk Between Cholesterol, ABC Transporters, and PIP2 in Inflammation and Atherosclerosis.Advances in experimental medicine and biology · 2023Article
- Genomic Analyses for Selective Signatures and Genes Involved in Hot Adaptation Among Indigenous Chickens From Different Tropical Climate Regions.Frontiers in genetics · 2022Article
- Sphingolipids and Asthma.Advances in experimental medicine and biology · 2022Article
- Expression Patterns and Prognostic Values of ORMDL1 in Different Cancers.BioMed research international · 2020Article
- Oxidized low-density lipoprotein inhibits the degradation of cyclophilin A via the lysosome in vascular smooth muscle cells.American journal of translational research · 2020Article
- Interplay Between Lipid Metabolism and Autophagy.Frontiers in cell and developmental biology · 2020Review
- ORMDL3 and allergic asthma: From physiology to pathology.The Journal of allergy and clinical immunology · 2019Review
- Endosome and Golgi-associated degradation (EGAD) of membrane proteins regulates sphingolipid metabolism.The EMBO journal · 2019Article
- Transmembrane topology of mammalian ORMDL proteins in the endoplasmic reticulum as revealed by the substituted cysteine accessibility method (SCAM™).Biochimica et biophysica acta. Proteins and proteomics · 2019Article
- The ORMDL/Orm-serine palmitoyltransferase (SPT) complex is directly regulated by ceramide: Reconstitution of SPT regulation in isolated membranes.The Journal of biological chemistry · 2019Article
- Associations ofArchives animal breeding · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Eukaryotic cells have evolved robust mechanisms to counter excess cholesterol including redistribution of lipids into different compartments and compensatory up-regulation of phospholipid biosynthesis. We demonstrate here that excess cellular cholesterol increased the activity of the endoplasmic reticulum (ER) enzyme serine palmitoyl-CoA transferase (SPT), the rate-limiting enzyme in sphingomyelin synthesis. This increased SPT activity was not due to altered levels of SPTLC1 or SPTLC2, the major subunits of SPT. Instead, cholesterol loading decreased the levels of ORMDL1, a negative regulator of SPT activity, due to its increased turnover. Several lines of evidence demonstrated that free-cholesterol-induced autophagy, which led to increased turnover of ORMDL1. Cholesterol loading induced ORMDL1 redistribution from the ER to cytoplasmic p62 positive autophagosomes. Coimmunoprecipitation analysis of cholesterol-loaded cells showed increased association between ORMDL1 and p62. The lysosomal inhibitor chloroquine or siRNA knockdown of Atg7 inhibited ORMDL1 degradation by cholesterol, whereas proteasome inhibitors showed no effect. ORMDL1 degradation was specific to free-cholesterol loading as autophagy induced by serum starvation or general ER stress did not lead to ORMDL1 degradation. ORMDL proteins are thus previously unidentified responders to excess cholesterol, exiting the ER to activate SPT and increase sphingomyelin biosynthesis, which may buffer excess cellular cholesterol.
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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.