Upregulated ethanolamine phospholipid synthesis via selenoprotein I is required for effective metabolic reprogramming during T cell activation
| Autor: | Vedbar S. Khadka, F. David Horgen, Sharon Rozovsky, Peter R. Hoffmann, Greg S. Gojanovich, Michael P. Marciel, Ellis N.L. Akana, Chi Ma, Melodie A. Williams-Aduja, Mariana Gerschenson, Johann Urschitz, FuKun W. Hoffmann, Stefan Moisyadi, Kathleen E. Page, Youping Deng |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male AMPK Glycosylphosphatidylinositols T-Lymphocytes Metabolic sensing chemistry.chemical_compound Mice 0302 clinical medicine Ethanolamine phosphotransferase Glycolysis Ethanolamine Selenoproteins SELENOI selenoprotein I Internal medicine Phospholipids chemistry.chemical_classification Mice Knockout AAG 1-alkyl acylglycerol TCR T cell receptor Cell biology medicine.anatomical_structure Ethanolamines E2F3 E2F transcription factor 3 Female Original Article Metabolic Networks and Pathways CDP cytidine 5-diphosphate GPI glycosylphosphatidylinositol T cell DEGs differentially expressed genes CCNE1 cyclin E1 PPP pentose phosphate pathway 030209 endocrinology & metabolism PE phosphatidylethanolamine Selenoprotein ER endoplasmic reticulum 03 medical and health sciences Selenium Downregulation and upregulation medicine Animals Metabolomics Molecular Biology CEPT1 choline/ethanolamine phosphotransferase 1 Cell Proliferation Phosphatidylethanolamine KO knockout Lipogenesis Phosphatidylethanolamines GPAA1 GPI anchor attachment protein 1 Cell Biology RC31-1245 WT wild-type Metabolic pathway AMPK AMP-activated protein kinase 030104 developmental biology Enzyme chemistry BUB1 benzimidazoles 1 Cancer cell DAG diacylglycerol |
| Zdroj: | Molecular Metabolism Molecular Metabolism, Vol 47, Iss, Pp 101170-(2021) |
| ISSN: | 2212-8778 |
| Popis: | Objective T cell activation triggers metabolic reprogramming to meet increased demands for energy and metabolites required for cellular proliferation. Ethanolamine phospholipid synthesis has emerged as a regulator of metabolic shifts in stem cells and cancer cells, which led us to investigate its potential role during T cell activation. Methods As selenoprotein I (SELENOI) is an enzyme participating in two metabolic pathways for the synthesis of phosphatidylethanolamine (PE) and plasmenyl PE, we generated SELENOI-deficient mouse models to determine loss-of-function effects on metabolic reprogramming during T cell activation. Ex vivo and in vivo assays were carried out along with metabolomic, transcriptomic, and protein analyses to determine the role of SELENOI and the ethanolamine phospholipids synthesized by this enzyme in cell signaling and metabolic pathways that promote T cell activation and proliferation. Results SELENOI knockout (KO) in mouse T cells led to reduced de novo synthesis of PE and plasmenyl PE during activation and impaired proliferation. SELENOI KO did not affect T cell receptor signaling, but reduced activation of the metabolic sensor AMPK. AMPK was inhibited by high [ATP], consistent with results showing SELENOI KO causing ATP accumulation, along with disrupted metabolic pathways and reduced glycosylphosphatidylinositol (GPI) anchor synthesis/attachment Conclusions T cell activation upregulates SELENOI-dependent PE and plasmenyl PE synthesis as a key component of metabolic reprogramming and proliferation. Highlights • Selenoprotein I is an enzyme that is upregulated during T cell activation. • Selenoprotein I catalyzes phospholipid synthesis to support proliferation. • Without increased phospholipid synthesis, metabolic shifts are impaired. • Selenoprotein I deficiency causes imbalanced metabolism and ATP accumulation. |
| Databáze: | OpenAIRE |
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