The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Why Do Cancers Have High Aerobic Glycolysis?
Gatenby, R. A., & Gillies, R. J. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1478 · Cited by 4,784
Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation
Lunt, S. Y., & Vander Heiden, M. G. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154237 · Cited by 3,057
The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth
Christofk, H. R., Vander Heiden, M. G., Harris, M. H., Ramanathan, A., Gerszten, R. E., Wei, R., Fleming, M. D., Schreiber, S. L., & Cantley, L. C. (2008) · Nature · doi:10.1038/nature06734 · Cited by 2,820
Brain energy metabolism: focus on Astrocyte-neuron metabolic cooperation
Bélanger, M., Allaman, I., & Magistretti, P. J. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.016 · Cited by 2,313
The Mystery and Magic of Glia: A Perspective on Their Roles in Health and Disease
Barres, B. A. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.013 · Cited by 1,352
The Retina: An Approachable Part of the Brain
(1989) · Archives of Ophthalmology · doi:10.1001/archopht.1989.01070020357018 · Cited by 1,124
Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis
Locasale, J. W., Grassian, A. R., Melman, T., Lyssiotis, C. A., Mattaini, K. R., Bass, A. J., Heffron, G., Metallo, C. M., Muranen, T., Sharfi, H., et al. (2011) · Nature Genetics · doi:10.1038/ng.890 · Cited by 1,120
Pyruvate kinase type M2 and its role in tumor growth and spreading
Mazurek, S., Boschek, C. B., Hugo, F., & Eigenbrodt, E. (2005) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2005.04.009 · Cited by 812
Tyrosine Phosphorylation Inhibits PKM2 to Promote the Warburg Effect and Tumor Growth
Hitosugi, T., Kang, S., Vander Heiden, M. G., Chung, T.-W., Elf, S., Lythgoe, K., Dong, S., Lonial, S., Wang, X., Chen, G. Z., et al. (2009) · Science Signaling · doi:10.1126/scisignal.2000431 · Cited by 784
Pellerin, L., & Magistretti, P. J. (2011) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2011.149 · Cited by 760
Cited by
Sorted by citations
Rod-Derived Cone Viability Factor Promotes Cone Survival by Stimulating Aerobic Glycolysis
Aït-Ali, N., Fridlich, R., Millet-Puel, G., Clérin, E., Delalande, F., Jaillard, C., Blond, F., Perrocheau, L., Reichman, S., Byrne, L. C., et al. (2015) · Cell · doi:10.1016/j.cell.2015.03.023 · Cited by 423
Kanow, M. A., Giarmarco, M. M., Jankowski, C. S., Tsantilas, K., Engel, A. L., Du, J., Linton, J. D., Farnsworth, C. C., Sloat, S. R., Rountree, A., et al. (2017) · eLife · doi:10.7554/elife.28899 · Cited by 377
Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism
Yellen, G. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201803152 · Cited by 371
“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).”
BackgroundMitochondrial complex I ROS production and redox signaling in hypoxia
Okoye, C. N., Koren, S. A., & Wojtovich, A. P. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102926 · Cited by 342
Lactate as a Metabolite and a Regulator in the Central Nervous System
Proia, P., Liegro, C. M. D., Schiera, G., Fricano, A., & Liegro, I. D. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17091450 · Cited by 290
Metadata
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
