Details

Autor(en) / Beteiligte

• Lindsay, Ken J.
• Du, Jianhai
• Sloat, Stephanie R.
• Contreras, Laura
• Linton, Jonathan D.
• Turner, Sally J.
• Sadilek, Martin
• Satrústegui, Jorgina
• Hurley, James B.

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2014-10, Vol.111 (43), p.15579-15584

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2014

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Symbiotic relationships between neurons and glia must adapt to structures, functions, and metabolic roles of the tissues they are in. We show here that Múííóóóéíóéóüüüller 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 Múííóóóéíóéóüüüüller cell’s ability to metabolize Glc. We show here that the cells can compensate for this deficiency by using metabolites produced by neurons. Múííóóóéíóéóüüüüüller 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. Múííóóóéíóéóüüüüüüller glia compensate for their unique metabolic adaptations by using lactate and aspartate from neurons as surrogates for their missing PK and AGC1. Significance Aerobic glycolysis is a metabolic adaptation that helps cells in a tumor meet high anabolic demands. The M2 isoform of pyruvate kinase (PKM2) is associated with aerobic glycolysis in cancer cells. Aerobic glycolysis also accounts for most of the Glc metabolized in retinas. We find that photoreceptors (PRs) in retinas, like cancer cells in tumors, express PKM2. We also found very little expression of pyruvate kinase (PK) in Múííóóóéíóéóüller glia. We present metabolic flux analyses that show a metabolic relationship between PRs and Múííóóóéíóéóüüller cells (MCs) that is different from the relationship between some neurons and astrocytes in brain. To compensate for PK deficiency and aspartate/glutamate carrier 1 deficiencies, MCs can fuel their mitochondria with lactate and aspartate produced by PRs.