Ammonia derived from glutaminolysis is a diffusible regulator of autophagy

Christina H. Eng, Ker Yu, Judy Lucas, Eileen White, Robert T. Abraham

Research output: Contribution to journalArticlepeer-review

252 Scopus citations


Autophagy is a tightly regulated catabolic process that plays key roles in normal cellular homeostasis and survival during periods of extracellular nutrient limitation and stress. The environmental signals that regulate autophagic activity are only partially understood. Here, we report a direct link between glutamine (Gln) metabolism and autophagic activity in both transformed and nontransformed human cells. Cells cultured for more than 2 days in Gln-containing medium showed increases in autophagy that were not attributable to nutrient depletion or to inhibition of mammalian target of rapamycin. Conditioned medium from these cells contained a volatile factor that triggered autophagy in secondary cell cultures. We identified this factor as ammonia derived from the deamination of Gln by glutaminolysis. Gln-dependent ammonia production supported basal autophagy and protected cells from tumor necrosis factor-α (TNF-α)-induced cell death. Thus, Gln metabolism not only fuels cell growth, but also generates an autocrine- and paracrine-acting regulator of autophagic flux in proliferating cells.

Original languageEnglish (US)
Pages (from-to)ra31
JournalScience signaling
Issue number119
StatePublished - Apr 27 2010

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Ammonia derived from glutaminolysis is a diffusible regulator of autophagy'. Together they form a unique fingerprint.

Cite this