GSEA of mouse and human mitochondriomes reveals fatty acid oxidation in astrocytes

Abel Eraso-Pichot; Marina Brasó-Vives; Arantxa Golbano; Carmen Menacho; Enrique Claro; Elena Galea; Roser Masgrau

GSEA of mouse and human mitochondriomes reveals fatty acid oxidation in astrocytes

Abel Eraso-Pichot, Marina Brasó-Vives, Arantxa Golbano, Carmen Menacho, Enrique Claro, Elena Galea, Roser Masgrau

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La visió predominant en neuroenergètica és que la glucosa és el principal combustible del cervell, i les neurones són majoritàriament oxidatives i els astròcits glicolítics. S'ha passat per alt l'evidència que dóna suport a la idea de què les mitocòndries dels astròcits funcionen. Aquí hem intentat determinar allò que és únic sobre les mitocòndries dels astròcits duent a terme comparacions estadístiques imparcials del mitocondrioma en els astròcits i neurones. Utilitzant MitoCarta, un compendi de proteïnes mitocondrials, juntament amb transcriptomes de neurones i astròcits de ratolí, hem generat bases de dades específiques de cèl·lules de gens nuclears que codifiquen per a les proteïnes del mitocondrioma, classificades segons l'expressió relativa. Les anàlisis estàndards i internes d'enriquiment de conjunts de gens (GSEA) de cinc transcriptomes de ratolins han revelat que els gens que codifiquen per enzims implicats en l'oxidació d'àcids grassos (FAO) i el catabolisme d'aminoàcids estan més ben expressades en astròcits que en neurones. Els gens FAO i relacionats amb el metabolisme oxidatiu també s'expressen de manera consistent en els astròcits humans, comparats amb la totalitat del còrtex, i en els astròcits adults versus fetals. Així doncs, presentem les primeres proves de la visió centrada en la glucosa del metabolisme energètic dels astròcits i revelem que les mitocòndries són orgànuls especialitzats d'aquestes cèl·lules. © 2018 Wiley Periodicals, Inc

Idioma original	Anglès
Pàgines (de-a)	1724-1735
Revista	Glia
Volum	66
Número	8
Estat de la publicació	Publicada - 1 d’ag. 2018

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@article{314b7396b6b541c2941ef64e83ed038e,

title = "GSEA of mouse and human mitochondriomes reveals fatty acid oxidation in astrocytes",

abstract = "{\textcopyright} 2018 Wiley Periodicals, Inc. 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.",

keywords = "metabolism, mitochondria, neurons, transcriptome",

author = "Abel Eraso-Pichot and Marina Bras{\'o}-Vives and Arantxa Golbano and Carmen Menacho and Enrique Claro and Elena Galea and Roser Masgrau",

year = "2018",

month = aug,

day = "1",

language = "English",

volume = "66",

pages = "1724--1735",

journal = "Glia",

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TY - JOUR

T1 - GSEA of mouse and human mitochondriomes reveals fatty acid oxidation in astrocytes

AU - Eraso-Pichot, Abel

AU - Brasó-Vives, Marina

AU - Golbano, Arantxa

AU - Menacho, Carmen

AU - Claro, Enrique

AU - Galea, Elena

AU - Masgrau, Roser

PY - 2018/8/1

Y1 - 2018/8/1

N2 - © 2018 Wiley Periodicals, Inc. 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.

AB - © 2018 Wiley Periodicals, Inc. 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.

KW - metabolism

KW - mitochondria

KW - neurons

KW - transcriptome

UR - https://www.scopus.com/pages/publications/85044379645

M3 - Article

SN - 0894-1491

VL - 66

SP - 1724

EP - 1735

JO - Glia

JF - Glia

IS - 8

ER -

GSEA of mouse and human mitochondriomes reveals fatty acid oxidation in astrocytes

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