Pyruvate kinase and aspartate-glutamate carrier distributions reveal key metabolic links between neurons and glia in retina
Open accessAbstract
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.
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Müller cells are deficient in pyruvate kinase, the final enzyme in the glycolytic pathway, and have limited ability to convert glucose to lactate.
“Müller cells are deficient in pyruvate kinase, the final enzyme in the glycolytic pathway, and have limited ability to convert glucose to lactate (Lindsay et al., 2014).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Lindsay et al., 2014
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- Authors
- Lindsay, K. J., Du, J., Sloat, S. R., Contreras, L., Linton, J. D., Turner, S. J., Sadilek, M., Satrústegui, J., & Hurley, J. B.
- Affiliations
- Departments of aBiochemistry,
- Consejo Superior de Investigaciones Científicas (ES)
- Chemistry and
- University of Washington (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-10-13
- Volume
- 111
- Issue
- 43
- Pages
- 15579-15584
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4217417
- OpenAlex
- W1968686900
- Cited by
- 131
- References
- 44
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 5 · 2023: 10 · 2022: 17 · 2021: 12 · 2020: 16 · 2019: 8 · 2018: 7 · 2017: 16 · 2016: 14 · 2015: 6 · 2013: 1
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Eye Institute (EY06641, R21EY023346, EY 1730, F32EY006641, EY023346, R01EY017863, R01EY006641, P30EY001730)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK017047)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- pyruvate kinase, Müller cells, retinal neurons, malate-aspartate shuttle, glutamine synthesis, glucose metabolism, lactate, photoreceptors, PKM2, retinal metabolism
- MeSH terms
- Animals, Aspartic Acid, Carbon Isotopes, Cells, Cultured, Glucose, Glutamine, Glycolysis, HeLa Cells, Humans, Isoenzymes, Lactose, Light, Models, Biological, Neuroglia, Oxidation-Reduction, Pyruvate Kinase, Antiporters, Photoreceptor Cells, Vertebrate, Amino Acid Transport Systems, Acidic, Mice, Retinal Neurons, Ependymoglial Cells
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