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Sci. Signal., 1 June 2010
Vol. 3, Issue 124, p. pe19
Ammonia: A Diffusible Factor Released by Proliferating Cells That Induces Autophagy
Guillermo Mariño and
INSERM, U848, F-94805 Villejuif, France; Institut Gustave Roussy, F-94805 Villejuif, France; and Université Paris Sud-XI, F-94805 Villejuif, France.
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.
Taro Hitosugi, Sumin Kang, Matthew G. Vander Heiden, Tae-Wook Chung, Shannon Elf, Katherine Lythgoe, Shaozhong Dong, Sagar Lonial, Xu Wang, Georgia Z. Chen, Jianxin Xie, Ting-Lei Gu, Roberto D. Polakiewicz, Johannes L. Roesel, Titus J. Boggon, Fadlo R. Khuri, D. Gary Gilliland, Lewis C. Cantley, Jonathan Kaufman, and Jing Chen (17 November 2009) Sci. Signal.2 (97), ra73.
[DOI: 10.1126/scisignal.2000431] |Editor's Summary »|Abstract »|Full Text »|PDF »|Supplementary Materials »
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|Abstract »|Full Text »|PDF »