title: Neuronal differentiation involves a shift from glucose oxidation to fermentation.
abstract: Energy metabolism in the adult brain consumes large quantities of glucose, but little is known to date regarding how glucose metabolism changes during neuronal differentiation, a process that is highly demanding energetically. We studied changes in glucose metabolism during neuronal differentiation of P19 mouse embryonal carcinoma cells, E14Tg2A embryonic stem cells as well as during brain development of BLC57 mice. In all these models, we find that neurogenesis is accompanied by a shift from oxidative to fermentative glucose metabolism. This shift is accompanied by both a decrease in mitochondrial enzymatic activities and mitochondrial uncoupling. In keeping with this finding, we also observe that differentiation does not require oxidative metabolism, as indicated by experiments demonstrating that the process is preserved in cells treated with the ATP synthase inhibitor oligomycin. Overall, we provide evidence that neuronal differentiation involves a shift from oxidative to fermentative metabolism, and that oxidative phosphorylation is not essential for this process.
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes 748, 05508-900 São Paulo, SP, Brazil.
authors.forename: Maynara
authors.initials: M
authors.lastname: Fornazari
authors.forename: Isis C
authors.initials: IC
authors.lastname: Nascimento
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Nery
authors.forename: Camille C Caldeira
authors.initials: CC
authors.lastname: da Silva
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Kowaltowski
authors.forename: Henning
authors.initials: H
authors.lastname: Ulrich
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D051379:Mice; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D010085:Oxidative Phosphorylation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D009840:Oligomycins; D025261:Mitochondrial Proton-Translocating ATPases; D005947:Glucose