ArticleJournal of lipid research2015
ORMDL/serine palmitoyltransferase stoichiometry determines effects of ORMDL3 expression on sphingolipid biosynthesis.
Article in Journal of lipid research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 64 citations in OpenAlex.
- Sphingolipids and Atherosclerosis.Current atherosclerosis reports · 2026Review
- 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
- Metabolic licensing at the dendritic cell-NK cells immune synapse in viral asthma exacerbations.Frontiers in immunology · 2026Review
- Expression levels ofHeliyon · 2024Article
- Fine-tuned protein-lipid interactions in biological membranes: exploration and implications of the ORMDL-ceramide negative feedback loop in the endoplasmic reticulum.Frontiers in cell and developmental biology · 2024Article
- Integrative single-cell analysis of LUAD: elucidating immune cell dynamics and prognostic modeling based on exhausted CD8+ T cells.Frontiers in immunology · 2024Article
- 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
- Sphingolipids in Childhood Asthma and Obesity (SOAP Study): A Protocol of a Cross-Sectional Study.Metabolites · 2023Article
- Ceramide sensing by human SPT-ORMDL complex for establishing sphingolipid homeostasis.Nature communications · 2023Article
- SPTSSA variants alter sphingolipid synthesis and cause a complex hereditary spastic paraplegia.Brain : a journal of neurology · 2023Article
- Mechanism of sphingolipid homeostasis revealed by structural analysis ofScience advances · 2023Article
- NJK14047 Suppression of the p38 MAPK Ameliorates OVA-Induced Allergic Asthma during Sensitization and Challenge Periods.Biomolecules & therapeutics · 2023Article
- Association of childhood asthma with Gasdermin B (GSDMB) and Oromucoid-like 3 (ORMDL3) genes.Northern clinics of Istanbul · 2023Article
- Article
- Targeting the Sphingolipid Rheostat in Gliomas.International journal of molecular sciences · 2022Review
- Human Rhinovirus Infection of the Respiratory Tract Affects Sphingolipid Synthesis.American journal of respiratory cell and molecular biology · 2022Article
- Sphingolipids and Asthma.Advances in experimental medicine and biology · 2022Article
- More Evidence for Inborn Dysregulation of Sphingolipid Metabolism in Children with Asthma?American journal of respiratory and critical care medicine · 2021Article
- Characteristics and Mechanisms of a Sphingolipid-associated Childhood Asthma Endotype.American journal of respiratory and critical care medicine · 2021Article
- Structural insights into the regulation of human serine palmitoyltransferase complexes.Nature structural & molecular biology · 2021Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The ORM1 (Saccharomyces cerevisiae)-like proteins (ORMDLs) and their yeast orthologs, the Orms, are negative homeostatic regulators of the initiating enzyme in sphingolipid biosynthesis, serine palmitoyltransferase (SPT). Genome-wide association studies have established a strong correlation between elevated expression of the endoplasmic reticulum protein ORMDL3 and risk for childhood asthma. Here we test the notion that elevated levels of ORMDL3 decrease sphingolipid biosynthesis. This was tested in cultured human bronchial epithelial cells (HBECs) (an immortalized, but untransformed, airway epithelial cell line) and in HeLa cells (a cervical adenocarcinoma cell line). Surprisingly, elevated ORMDL3 expression did not suppress de novo biosynthesis of sphingolipids. We determined that ORMDL is expressed in functional excess relative to SPT at normal levels of expression. ORMDLs and SPT form stable complexes that are not increased by elevated ORMDL3 expression. Although sphingolipid biosynthesis was not decreased by elevated ORMDL3 expression, the steady state mass levels of all major sphingolipids were marginally decreased by low level ORMDL3 over-expression in HBECs. These data indicate that the contribution of ORMDL3 to asthma risk may involve changes in sphingolipid metabolism, but that the connection is complex.
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