title: Pyruvate kinase and aspartate-glutamate carrier distributions reveal key metabolic links between neurons and glia in retina.
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.
authors.affiliation: Departments of Biochemistry.
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Lindsay
authors.affiliation: Departments of Biochemistry.
authors.forename: Jianhai
authors.initials: J
authors.lastname: Du
authors.affiliation: Departments of Biochemistry.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Sloat
authors.affiliation: Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa Universidad Autónoma-Consejo Superior de Investigaciones Cientificas, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, and Centro de Investigación Biomédica en Red de Enfermedades Raras, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Contreras
authors.affiliation: Departments of Biochemistry.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Linton
authors.affiliation: Departments of Biochemistry.
authors.forename: Sally J
authors.initials: SJ
authors.lastname: Turner
authors.affiliation: Chemistry and.
authors.forename: Martin
authors.initials: M
authors.lastname: Sadilek
authors.affiliation: Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa Universidad Autónoma-Consejo Superior de Investigaciones Cientificas, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, and Centro de Investigación Biomédica en Red de Enfermedades Raras, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Jorgina
authors.identifier: http://orcid.org/0000-0002-7741-9366
authors.initials: J
authors.lastname: Satrústegui
authors.affiliation: Departments of Biochemistry, Ophthalmology, University of Washington, Seattle, WA 98195; and jbhhh@uw.edu.
authors.forename: James B
authors.initials: JB
authors.lastname: Hurley
mesh_terms: D026922:Amino Acid Transport Systems, Acidic / Q000378:metabolism*; D000818:Animals; D017920:Antiporters / Q000378:metabolism*; D001224:Aspartic Acid / Q000378:metabolism; D002247:Carbon Isotopes; D002478:Cells, Cultured; D063928:Ependymoglial Cells / Q000378:metabolism / Q000528:radiation effects; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006019:Glycolysis; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007785:Lactose / Q000378:metabolism; D008027:Light; D051379:Mice; D008954:Models, Biological; D009457:Neuroglia / Q000378:metabolism* / Q000528:radiation effects; D010084:Oxidation-Reduction / Q000528:radiation effects; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000528:radiation effects; D011770:Pyruvate Kinase / Q000378:metabolism*; D055351:Retinal Neurons / Q000378:metabolism* / Q000528:radiation effects
chemical_list: D026922:Amino Acid Transport Systems, Acidic; D017920:Antiporters; D002247:Carbon Isotopes; D007527:Isoenzymes; C051046:aspartate-glutamate carrier; D005973:Glutamine; D001224:Aspartic Acid; D011770:Pyruvate Kinase; D005947:Glucose; D007785:Lactose
keywords: Müller glia; aerobic glycolysis; glutamine metabolism; photoreceptors; retina