PerspectiveCell Biology

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

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Sci. Signal.  01 Jun 2010:
Vol. 3, Issue 124, pp. pe19
DOI: 10.1126/scisignal.3124pe19

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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.

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