Cited by 131Retinal Development and DisordersNeuroscience and Neuropharmacology ResearchCancer, Hypoxia, and Metabolism

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

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Lindsay, Ken J., Du, Jianhai, Sloat, Stephanie R., Contreras, Laura, Linton, Jonathan D., Turner, Sally J., Sadilek, Martin, Satrústegui, Jorgina, Hurley, James B.·2014·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1412441111PMC PMC4217417

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Abstract

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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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)
ORCID: Du, Jianhai
Contreras, Laura
Satrústegui, Jorgina
Hurley, James B.
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
DOI: 10.1073/pnas.1412441111
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
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: Health Sciences › Medicine › Ophthalmology › 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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Pyruvate kinase and aspartate-glutamate carrier distributions reveal key metabolic links between neurons and glia in retina

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