Nature Chemical Biology
Nature Chemical Biology
5 years ago

Extracellular vesicles are independent metabolic units with asparaginase activity

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

Publisher URL: http://dx.doi.org/10.1038/nchembio.2422

DOI: 10.1038/nchembio.2422

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