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Ammonia: a diffusible factor released by proliferating cells that induces autophagy
Guillermo Mariño1, Guido Kroemer
1INSERM, U848, Villejuif, France.
Science Signaling
|June 3, 2010
Summary
Ammonia, a byproduct of glutaminolysis, stimulates autophagy, a cellular digestion process. Cancer cells utilize this pathway, increasing ammonia levels to influence their microenvironment.
Area of Science:
- Cellular Biology
- Biochemistry
- Cancer Research
Background:
- Autophagy is a fundamental cellular process where cytoplasm is degraded within lysosomes.
- Nutrient deprivation can induce autophagy in mammalian tissues, stimulating research into autophagy-modulating metabolites.
- Glutaminolysis, a metabolic pathway, generates ammonia as a byproduct.
Purpose of the Study:
- To identify soluble metabolites that can stimulate autophagy.
- To investigate the role of ammonia in autophagy.
- To explore the potential of ammonia in cancer cell-mediated microenvironment conditioning.
Main Methods:
- Investigated the role of ammonia as a diffusible factor in stimulating autophagy.
- Analyzed glutaminolysis rates in cancer cells.
- Measured ammonia concentrations in the interstitial fluid of tumors.
Main Results:
- Ammonia was identified as a diffusible factor that stimulates autophagy.
- Cancer cells exhibit increased rates of glutaminolysis.
- Elevated physiological concentrations of ammonia were found in the interstitial fluid of cancers.
Conclusions:
- Ammonia directly stimulates autophagy.
- Cancer cells leverage glutaminolysis to produce ammonia, influencing their surrounding microenvironment.
- This represents a novel pathway for tumor cells to condition their microenvironment.
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