Ammonia: a diffusible factor released by proliferating cells that induces autophagy
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Updated: Jun 12, 2026

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
Published on: January 31, 2025
Guillermo Mariño1, Guido Kroemer
1INSERM, U848, 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.
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