Pyruvate kinase and aspartate-glutamate carrier distributions reveal key metabolic links between neurons and glia in retina

Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15579-84. doi: 10.1073/pnas.1412441111. Epub 2014 Oct 13.


Symbiotic relationships between neurons and glia must adapt to structures, functions, and metabolic roles of the tissues they are in. We show here that Müller glia in retinas have specific enzyme deficiencies that can enhance their ability to synthesize Gln. The metabolic cost of these deficiencies is that they impair the Müller cell's ability to metabolize Glc. We show here that the cells can compensate for this deficiency by using metabolites produced by neurons. Müller glia are deficient for pyruvate kinase (PK) and for aspartate/glutamate carrier 1 (AGC1), a key component of the malate-aspartate shuttle. In contrast, photoreceptor neurons express AGC1 and the M2 isoform of pyruvate kinase, which is commonly associated with aerobic glycolysis in tumors, proliferating cells, and some other cell types. Our findings reveal a previously unidentified type of metabolic relationship between neurons and glia. Müller glia compensate for their unique metabolic adaptations by using lactate and aspartate from neurons as surrogates for their missing PK and AGC1.

Keywords: Müller glia; aerobic glycolysis; glutamine metabolism; photoreceptors; retina.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems, Acidic / metabolism*
  • Animals
  • Antiporters / metabolism*
  • Aspartic Acid / metabolism
  • Carbon Isotopes
  • Cells, Cultured
  • Ependymoglial Cells / metabolism
  • Ependymoglial Cells / radiation effects
  • Glucose / metabolism
  • Glutamine / metabolism
  • Glycolysis
  • HeLa Cells
  • Humans
  • Isoenzymes / metabolism
  • Lactose / metabolism
  • Light
  • Mice
  • Models, Biological
  • Neuroglia / metabolism*
  • Neuroglia / radiation effects
  • Oxidation-Reduction / radiation effects
  • Photoreceptor Cells, Vertebrate / metabolism
  • Photoreceptor Cells, Vertebrate / radiation effects
  • Pyruvate Kinase / metabolism*
  • Retinal Neurons / metabolism*
  • Retinal Neurons / radiation effects


  • Amino Acid Transport Systems, Acidic
  • Antiporters
  • Carbon Isotopes
  • Isoenzymes
  • aspartate-glutamate carrier
  • Glutamine
  • Aspartic Acid
  • Pyruvate Kinase
  • Glucose
  • Lactose