Extracellular vesicles are independent metabolic units with asparaginase activity

Nunzio Iraci, Edoardo Gaude, Tommaso Leonardi, Ana S.H. Costa, Chiara Cossetti, Luca Peruzzotti-Jametti, Joshua D. Bernstock, Harpreet K. Saini, Maurizio Gelati, Angelo Luigi Vescovi, Carlos Bastos, Nuno Faria, Luigi G. Occhipinti, Anton J. Enright, Christian Frezza, Stefano Pluchino

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Extracellular vesicles (EVs) are membrane particles involved in the exchange of a broad range of bioactive molecules between cells and the microenvironment. Although it has been shown that cells can traffic metabolic enzymes via EVs, much remains to be elucidated with regard to their intrinsic metabolic activity. Accordingly, herein we assessed the ability of neural stem/progenitor cell (NSC)-derived EVs to consume and produce metabolites. Our metabolomics and functional analyses both revealed that EVs harbor L-asparaginase activity, catalyzed by the enzyme asparaginase-like protein 1 (Asrgl1). Critically, we show that Asrgl1 activity is selective for asparagine and is devoid of glutaminase activity. We found that mouse and human NSC EVs traffic Asrgl1. Our results demonstrate, for the first time, that NSC EVs function as independent metabolic units that are able to modify the concentrations of critical nutrients, with the potential to affect the physiology of their microenvironment.

Original languageEnglish (US)
Pages (from-to)951-955
Number of pages5
JournalNature Chemical Biology
Volume13
Issue number9
DOIs
StatePublished - Sep 1 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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