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Sci. Signal., 1 June 2010
Vol. 3, Issue 124, p. pe19
[DOI: 10.1126/scisignal.3124pe19]


Ammonia: A Diffusible Factor Released by Proliferating Cells That Induces Autophagy

Guillermo Mariño and Guido Kroemer*

INSERM, U848, F-94805 Villejuif, France; Institut Gustave Roussy, F-94805 Villejuif, France; and Université Paris Sud-XI, F-94805 Villejuif, France.

Abstract: During autophagy, portions of the cytoplasm are sequestered into autophagosomes and digested by lysosomal hydrolases. Massive autophagy can be induced in mammalian tissues in a coordinated fashion through nutrient deprivation, which has prompted the search of soluble metabolites that can stimulate autophagy. Ammonia, which is generated as a by-product of glutaminolysis, has been identified as a diffusible factor that stimulates autophagy. Intriguingly, cancer cells increase the rate glutaminolysis and the interstitial fluid of cancers contains higher-than-normal physiological concentrations of ammonia, suggesting a previously unknown pathway through which tumor cells can condition their microenvironment.

* Corresponding author. E-mail: kroemer{at}

Citation: G. Mariño, G. Kroemer, Ammonia: A Diffusible Factor Released by Proliferating Cells That Induces Autophagy. Sci. Signal. 3, pe19 (2010).

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