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}orange.fr

The editors suggest the following Related Resources on Science sites:

In Science Signaling

EDITORIAL GUIDES
Cell Biology
2010: Signaling Breakthroughs of the Year

Elizabeth M. Adler (4 January 2011)
Sci. Signal. 4 (154), eg1. [DOI: 10.1126/scisignal.2001770]
 |  Abstract »  |  Full Text »  |  PDF »

EDITORIAL GUIDES
Cell Biology
Focus Issue: Metabolic Signals

Wei Wong (7 December 2010)
Sci. Signal. 3 (151), eg12. [DOI: 10.1126/scisignal.3151eg12]
 |  Abstract »  |  Full Text »  |  PDF »

EDITORS' CHOICE
Cell Biology
Degraded but not Dishevelled

Wei Wong (10 August 2010)
Sci. Signal. 3 (134), ec244. [DOI: 10.1126/scisignal.3134ec244]
 |  Abstract »

RESEARCH ARTICLES
Cell Biology
Ammonia Derived from Glutaminolysis Is a Diffusible Regulator of Autophagy

Christina H. Eng, Ker Yu, Judy Lucas, Eileen White, and Robert T. Abraham (27 April 2010)
Sci. Signal. 3 (119), ra31. [DOI: 10.1126/scisignal.2000911]
 |  Editor's Summary »  |  Abstract »  |  Full Text »  |  PDF »  |  Supplementary Materials »

PERSPECTIVES
Cancer
PKM2 Tyrosine Phosphorylation and Glutamine Metabolism Signal a Different View of the Warburg Effect

Chi V. Dang (17 November 2009)
Sci. Signal. 2 (97), pe75. [DOI: 10.1126/scisignal.297pe75]
 |  Abstract »  |  Full Text »  |  PDF »

RESEARCH ARTICLES
Cancer
Tyrosine Phosphorylation Inhibits PKM2 to Promote the Warburg Effect and Tumor Growth

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 »

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES: