GSEA of mouse and human mitochondriomes reveals fatty acid oxidation in astrocytes
Eraso-Pichot, Abel (Universitat Autònoma de Barcelona. Institut de Neurociències)
Brasó-Vives, Marina (Institut de Biologia Evolutiva (UPF-CSIC) (Barcelona))
Golbano Rodríguez, Arantxa (Universitat Autònoma de Barcelona. Institut de Neurociències)
Menacho, Carmen (Universitat Autònoma de Barcelona. Institut de Neurociències)
Galea, Elena (Universitat Autònoma de Barcelona. Institut de Neurociències)
Claro Izaguirre, Enrique (Universitat Autònoma de Barcelona. Institut de Neurociències)
Masgrau Juanola, Roser (Universitat Autònoma de Barcelona. Institut de Neurociències)

Date:	2018
Abstract:	The prevalent view in neuroenergetics is that glucose is the main brain fuel, with neurons being mostly oxidative and astrocytes glycolytic. Evidence supporting that astrocyte mitochondria are functional has been overlooked. Here we sought to determine what is unique about astrocyte mitochondria by performing unbiased statistical comparisons of the mitochondriome in astrocytes and neurons. Using MitoCarta, a compendium of mitochondrial proteins, together with transcriptomes of mouse neurons and astrocytes, we generated cell-specific databases of nuclear genes encoding for mitochondrion proteins, ranked according to relative expression. Standard and in-house Gene Set Enrichment Analyses (GSEA) of five mouse transcriptomes revealed that genes encoding for enzymes involved in fatty acid oxidation (FAO) and amino acid catabolism are consistently more expressed in astrocytes than in neurons. FAO and oxidative-metabolism-related genes are also up-regulated in human cortical astrocytesversus the whole cortex, and in adult astrocytes versus fetal astrocytes. We thus present the first evidence of FAO in human astrocytes. Further, as shown in vitro, FAO coexists with glycolysis in astrocytes and is inhibited by glutamate. Altogether, these analyses provide arguments against the glucose-centered view of energy metabolism in astrocytes and reveal mitochondria as specialized organelles in these cells.
Grants:	Agència de Gestió d'Ajuts Universitaris i de Recerca FI_B 00730 Ministerio de Economía y Competitividad BFU2012-38844 Ministerio de Economía y Competitividad BFU2016-79735-P Ministerio de Educación, Cultura y Deporte FPU13/05377
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Metabolism ; Mitochondria ; Neurons ; Transcriptome
Published in:	GLIA, Vol. 66 Núm. 8 (2018) , p. 1724-1735, ISSN 1098-1136

DOI: 10.1002/glia.23330

24 p, 639.7 KB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles