Enhanced phosphocholine metabolism is essential for terminal erythropoiesis
Red cells contain a unique constellation of membrane lipids. Although much is known about regulated protein expression, the regulation of lipid metabolism during erythropoiesis is poorly studied. Here, we show that transcription of PHOSPHO1, a phosphoethanolamine and phosphocholine phosphatase that...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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American Society of Hematology
2020
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| Online Access: | https://hdl.handle.net/1721.1/125205 |
| _version_ | 1826192790010200064 |
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| author | Huang, Nai-Jia Lin, Chung-Yueh Pishesha, Novalia Lewis, Caroline A. Freinkman, Elizaveta Lodish, Harvey |
| author2 | Whitehead Institute for Biomedical Research |
| author_facet | Whitehead Institute for Biomedical Research Huang, Nai-Jia Lin, Chung-Yueh Pishesha, Novalia Lewis, Caroline A. Freinkman, Elizaveta Lodish, Harvey |
| author_sort | Huang, Nai-Jia |
| collection | MIT |
| description | Red cells contain a unique constellation of membrane lipids. Although much is known about regulated protein expression, the regulation of lipid metabolism during erythropoiesis is poorly studied. Here, we show that transcription of PHOSPHO1, a phosphoethanolamine and phosphocholine phosphatase that mediates the hydrolysis of phosphocholine to choline, is strongly upregulated during the terminal stages of erythropoiesis of both human and mouse erythropoiesis, concomitant with increased catabolism of phosphatidylcholine (PC) and phosphocholine as shown by global lipidomic analyses of mouse and human terminal erythropoiesis. Depletion of PHOSPHO1 impaired differentiation of fetal mouse and human erythroblasts, and, in adult mice, depletion impaired phenylhydrazine-induced stress erythropoiesis. Loss of PHOSPHO1 also impaired phosphocholine catabolism in mouse fetal liver progenitors and resulted in accumulation of several lipids; adenosine triphosphate (ATP) production was reduced as a result of decreased oxidative phosphorylation. Glycolysis replaced oxidative phosphorylation in PHOSPHO1-knockout erythroblasts and the increased glycolysis was used for the production of serine or glycine. Our study elucidates the dynamic changes in lipid metabolism during terminal erythropoiesis and reveals the key roles of PC and phosphocholine metabolism in energy balance and amino acid supply. |
| first_indexed | 2024-09-23T09:29:14Z |
| format | Article |
| id | mit-1721.1/125205 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:29:14Z |
| publishDate | 2020 |
| publisher | American Society of Hematology |
| record_format | dspace |
| spelling | mit-1721.1/1252052022-09-26T11:43:19Z Enhanced phosphocholine metabolism is essential for terminal erythropoiesis Huang, Nai-Jia Lin, Chung-Yueh Pishesha, Novalia Lewis, Caroline A. Freinkman, Elizaveta Lodish, Harvey Whitehead Institute for Biomedical Research Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Red cells contain a unique constellation of membrane lipids. Although much is known about regulated protein expression, the regulation of lipid metabolism during erythropoiesis is poorly studied. Here, we show that transcription of PHOSPHO1, a phosphoethanolamine and phosphocholine phosphatase that mediates the hydrolysis of phosphocholine to choline, is strongly upregulated during the terminal stages of erythropoiesis of both human and mouse erythropoiesis, concomitant with increased catabolism of phosphatidylcholine (PC) and phosphocholine as shown by global lipidomic analyses of mouse and human terminal erythropoiesis. Depletion of PHOSPHO1 impaired differentiation of fetal mouse and human erythroblasts, and, in adult mice, depletion impaired phenylhydrazine-induced stress erythropoiesis. Loss of PHOSPHO1 also impaired phosphocholine catabolism in mouse fetal liver progenitors and resulted in accumulation of several lipids; adenosine triphosphate (ATP) production was reduced as a result of decreased oxidative phosphorylation. Glycolysis replaced oxidative phosphorylation in PHOSPHO1-knockout erythroblasts and the increased glycolysis was used for the production of serine or glycine. Our study elucidates the dynamic changes in lipid metabolism during terminal erythropoiesis and reveals the key roles of PC and phosphocholine metabolism in energy balance and amino acid supply. United States. Defense Advanced Research Projects Agency (Contract HR0011-14-2-0005) National Heart, Lung, and Blood Institute (Grant 2 P01 HL032262-25) 2020-05-13T14:10:46Z 2020-05-13T14:10:46Z 2018-06 2020-01-24T18:25:30Z Article http://purl.org/eprint/type/JournalArticle 0006-4971 https://hdl.handle.net/1721.1/125205 Huang, Nai-Jia et al. “Enhanced phosphocholine metabolism is essential for terminal erythropoiesis.” Blood 131 (2018): 2955-2966 © 2018 The Author(s) en 10.1182/BLOOD-2018-03-838516 Blood Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Society of Hematology Other repository |
| spellingShingle | Huang, Nai-Jia Lin, Chung-Yueh Pishesha, Novalia Lewis, Caroline A. Freinkman, Elizaveta Lodish, Harvey Enhanced phosphocholine metabolism is essential for terminal erythropoiesis |
| title | Enhanced phosphocholine metabolism is essential for terminal erythropoiesis |
| title_full | Enhanced phosphocholine metabolism is essential for terminal erythropoiesis |
| title_fullStr | Enhanced phosphocholine metabolism is essential for terminal erythropoiesis |
| title_full_unstemmed | Enhanced phosphocholine metabolism is essential for terminal erythropoiesis |
| title_short | Enhanced phosphocholine metabolism is essential for terminal erythropoiesis |
| title_sort | enhanced phosphocholine metabolism is essential for terminal erythropoiesis |
| url | https://hdl.handle.net/1721.1/125205 |
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