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

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 Müller glia. We present metabolic flux analyses that show a metabolic relationship between PRs and Müller 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.