Enhanced phosphocholine metabolism is essential for terminal erythropoiesis

Nai-Jia Huang, Ying-Cing Lin, Chung-Yueh Lin, Novalia Pishesha, Caroline A Lewis, Elizaveta Freinkman, Colin Farquharson, José Luis Millán, Harvey Lodish

Research output: Contribution to journalArticlepeer-review

Abstract

Red cells contain a unique constellation of membrane lipids. While 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 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; 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 phosphatidylcholine and phosphocholine metabolism in energy balance and amino acid supply.

Original languageEnglish
Pages (from-to)2955-2966
JournalBlood
Volume131
Issue number26
Early online date30 Apr 2018
DOIs
Publication statusPublished - 28 Jun 2018

Keywords

  • ERYTHROPOIESIS
  • PHOSPHO1
  • phosphocholine

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