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Enhanced phosphocholine metabolism is essential for terminal erythropoiesis

Author(s)
Huang, Nai-Jia; Lin, Chung-Yueh; Pishesha, Novalia; Lewis, Caroline A.; Freinkman, Elizaveta; Lodish, Harvey; ... Show more Show less
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Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/
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Abstract
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.
Date issued
2018-06
URI
https://hdl.handle.net/1721.1/125205
Department
Whitehead Institute for Biomedical Research; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Biology
Journal
Blood
Publisher
American Society of Hematology
Citation
Huang, Nai-Jia et al. “Enhanced phosphocholine metabolism is essential for terminal erythropoiesis.” Blood 131 (2018): 2955-2966 © 2018 The Author(s)
Version: Author's final manuscript
ISSN
0006-4971

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