Human retinal pigment epithelial cells prefer proline as a nutrient and transport metabolic intermediates to the retinal side

Jennifer R. Chao, Kaitlen Knight, Abbi L. Engel, Connor Jankowski, Yekai Wang, Megan A. Manson, Haiwei Gu, Danijel Djukovic, Daniel Raftery, James B. Hurley, Jianhai Du

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Metabolite transport is a major function of the retinal pigment epithelium (RPE) to support the neural retina. RPE dysfunction plays a significant role in retinal degenerative diseases. We have used mass spectrometry with 13C tracers to systematically study nutrient consumption and metabolite transport in cultured human fetal RPE. LC/MS-MS detected 120 metabolites in the medium from either the apical or basal side. Surprisingly, more proline is consumed than any other nutrient, including glucose, taurine, lipids, vitamins, or other amino acids. Besides being oxidized through the Krebs cycle, proline is used to make citrate via reductive carboxylation. Citrate, made either from 13C proline or from 13C glucose, is preferentially exported to the apical side and is taken up by the retina. In conclusion, RPE cells consume multiple nutrients, including glucose and taurine, but prefer proline, and they actively synthesize and export metabolic intermediates to the apical side to nourish the outer retina.

Original languageEnglish (US)
Pages (from-to)12895-12905
Number of pages11
JournalJournal of Biological Chemistry
Volume292
Issue number31
DOIs
StatePublished - Aug 4 2017
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Chao, J. R., Knight, K., Engel, A. L., Jankowski, C., Wang, Y., Manson, M. A., Gu, H., Djukovic, D., Raftery, D., Hurley, J. B., & Du, J. (2017). Human retinal pigment epithelial cells prefer proline as a nutrient and transport metabolic intermediates to the retinal side. Journal of Biological Chemistry, 292(31), 12895-12905. https://doi.org/10.1074/jbc.M117.788422