Ammonia: a diffusible factor released by proliferating cells that induces autophagy

Sci Signal. 2010 Jun 1;3(124):pe19. doi: 10.1126/scisignal.3124pe19.


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.

Publication types

  • Review

MeSH terms

  • Ammonia / metabolism*
  • Animals
  • Autophagy*
  • Cell Proliferation*
  • Glutamine / metabolism*
  • Humans
  • Hydrolases / metabolism
  • Lysosomes / metabolism*
  • Neoplasms / metabolism*


  • Glutamine
  • Ammonia
  • Hydrolases