title: Neuronal Progenitor Maintenance Requires Lactate Metabolism and PEPCK-M-Directed Cataplerosis.
abstract: This study investigated the metabolic requirements for neuronal progenitor maintenance in vitro and in vivo by examining the metabolic adaptations that support neuronal progenitors and neural stem cells (NSCs) in their undifferentiated state. We demonstrate that neuronal progenitors are strictly dependent on lactate metabolism, while glucose induces their neuronal differentiation. Lactate signaling is not by itself capable of maintaining the progenitor phenotype. The consequences of lactate metabolism include increased mitochondrial and oxidative metabolism, with a strict reliance on cataplerosis through the mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) pathway to support anabolic functions, such as the production of extracellular matrix. In vivo, lactate maintains/induces populations of postnatal neuronal progenitors/NSCs in a PEPCK-M-dependent manner. Taken together, our data demonstrate that, lactate alone or together with other physical/biochemical cues maintain NSCs/progenitors with a metabolic signature that is classically found in tissues with high anabolic capacity.
authors.affiliation: Institute for Bioengineering of Catalonia-IBEC, Barcelona, Spain Department of Pathology and Experimental Therapeutics CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain.
authors.forename: Zaida
authors.initials: Z
authors.lastname: Álvarez
authors.affiliation: Department of Physiological Sciences II, Medical School (Bellvitge Campus), University of Barcelona-UB, Barcelona, Spain.
authors.forename: Petra
authors.initials: P
authors.lastname: Hyroššová
authors.affiliation: Department of Physiological Sciences II, Medical School (Bellvitge Campus), University of Barcelona-UB, Barcelona, Spain.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Perales
authors.affiliation: Department of Pathology and Experimental Therapeutics.
authors.forename: Soledad
authors.initials: S
authors.lastname: Alcántara
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000255:Adenosine Triphosphate; D001973:Bromodeoxyuridine; D005947:Glucose; D019344:Lactic Acid; D019764:Phosphoenolpyruvate Carboxykinase (ATP); C000611827:Pck2 protein, mouse
keywords: PEPCK-M; lactate; metabolism; neural progenitors; neurons