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Title: p73 Regulates Primary Cortical Neuron Metabolism: a Global Metabolic Profile.
Authors: Agostini, Massimiliano
Niklison-Chirou, Maria Victoria
Annicchiarico-Petruzzelli, Margherita Maria
Grelli, Sandro
Di Daniele, Nicola
Pestlikis, Ilias
Knight, Richard A.
Melino, Gerry
Rufini, Alessandro
First Published: 6-May-2017
Publisher: Humana Press
Citation: Molecular Neurobiology, 2017
Abstract: The transcription factor p73 has been demonstrated to play a significant role in survival and differentiation of neuronal stem cells. In this report, by employing comprehensive metabolic profile and mitochondrial bioenergetics analysis, we have explored the metabolic alterations in cortical neurons isolated from p73 N-terminal isoform specific knockout animals. We found that loss of the TAp73 or ΔNp73 triggers selective biochemical changes. In particular, p73 isoforms regulate sphingolipid and phospholipid biochemical pathway signaling. Indeed, sphinganine and sphingosine levels were reduced in p73-depleted cortical neurons, and decreased levels of several membrane phospholipids were also observed. Moreover, in line with the complexity associated with p73 functions, loss of the TAp73 seems to increase glycolysis, whereas on the contrary, loss of ΔNp73 isoform reduces glucose metabolism, indicating an isoform-specific differential effect on glycolysis. These changes in glycolytic flux were not reflected by parallel alterations of mitochondrial respiration, as only a slight increase of mitochondrial maximal respiration was observed in p73-depleted cortical neurons. Overall, our findings reinforce the key role of p73 in regulating cellular metabolism and point out that p73 exerts its functions in neuronal biology at least partially through the regulation of metabolic pathways.
DOI Link: 10.1007/s12035-017-0517-3
ISSN: 0893-7648
eISSN: 1559-1182
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2017, Humana Press. Deposited with reference to the publisher’s open access archiving policy.
Description: The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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