p73 Regulates Primary Cortical Neuron Metabolism: a Global Metabolic Profile

Massimiliano Agostini, Maria Victoria Niklison-Chirou, Margherita Maria Annicchiarico-Petruzzelli, Sandro Grelli, Nicola Di Daniele, Ilias Pestlikis, Richard A. Knight, Gerry Melino, Alessandro Rufini

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3237-3250
Number of pages14
JournalMolecular Neurobiology
Volume55
Issue number4
DOIs
Publication statusPublished - Apr 1 2018

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Keywords

  • Metabolism
  • Neurons
  • p53 family
  • p73
  • Sphingolipids

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Agostini, M., Niklison-Chirou, M. V., Annicchiarico-Petruzzelli, M. M., Grelli, S., Di Daniele, N., Pestlikis, I., Knight, R. A., Melino, G., & Rufini, A. (2018). p73 Regulates Primary Cortical Neuron Metabolism: a Global Metabolic Profile. Molecular Neurobiology, 55(4), 3237-3250. https://doi.org/10.1007/s12035-017-0517-3