GSEA of mouse and human mitochondriomes reveals fatty acid oxidation in astrocytes
Glia. 2018-03-25; 66(8): 1724-1735
DOI: 10.1002/glia.23330
Lire sur PubMed
1. Glia. 2018 Aug;66(8):1724-1735. doi: 10.1002/glia.23330. Epub 2018 Mar 25.
GSEA of mouse and human mitochondriomes reveals fatty acid oxidation in
astrocytes.
Eraso-Pichot A(1), Brasó-Vives M(2), Golbano A(1), Menacho C(1), Claro E(1),
Galea E(1)(3), Masgrau R(1).
Author information:
(1)Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica de
Medicina, i Institut de Neurociències, Universitat Autònoma de Barcelona,
Barcelona, 08193, Spain.
(2)Institute of Evolutionary Biology (Universitat Pompeu Fabra – CSIC), PRBB,
Barcelona, 08003, Spain.
(3)ICREA, Passeig Lluís Companys 23, Barcelona, 08010, Spain.
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 astrocytes versus 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.
© 2018 Wiley Periodicals, Inc.
DOI: 10.1002/glia.23330
PMID: 29575211 [Indexed for MEDLINE]