Glutaminolysis yields a metabolic by-product that stimulates autophagy
Open accessAbstract
Autophagy is an intracellular degradative pathway that plays key roles in the homeostatic turnover of long-lived or damaged proteins and organelles, and in the survival of cells during starvation or other stressful conditions. We have uncovered an unexpected link between glutamine (Gln) metabolism and the regulation of autophagy. Our findings indicate that ammonia, generated from Gln deamination in mitochondria, functions as an autocrine- and/or paracrine-acting stimulator of autophagic flux.
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Glutamine metabolism plays a critical role in tumor progression by supporting mitochondrial oxidative phosphorylation, supplying TCA cycle intermediates, glutathione synthesis, NEAA synthesis, and producing NADPH.
“Unsurprisingly, glutamine metabolism plays a critical role in tumor progression since it not only supports mitochondrial oxidative phosphorylation but also supplies metabolic intermediates for the TCA cycle, glutathione synthesis, and NEAA synthesis and simultaneously produces NADPH157–159.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [158]
Cites
Ammonia Derived from Glutaminolysis Is a Diffusible Regulator of Autophagy
Eng, C. H., Yu, K., Lucas, J., White, E., & Abraham, R. T. (2010) · Science Signaling · doi:10.1126/scisignal.2000911 · Cited by 334 · see citing works
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Emerging regulation and functions of autophagy
Boya, P., Reggiori, F., & Codogno, P. (2013) · Nature Cell Biology · doi:10.1038/ncb2788 · Cited by 1,216 · see citing works
Glutamine reliance in cell metabolism
Yoo, H. C., Yu, Y. C., Sung, Y., & Han, J. M. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00504-8 · Cited by 1,021 · see citing works
SIRT5 regulation of ammonia-induced autophagy and mitophagy
Polletta, L., Vernucci, E., Carnevale, I., Arcangeli, T., Rotili, D., Palmerio, S., Steegborn, C., Nowak, T., Schutkowski, M., Pellegrini, L., et al. (2015) · Autophagy · doi:10.1080/15548627.2015.1009778 · Cited by 350 · see citing works
Martinez-Outschoorn, U. E., Pavlides, S., Howell, A., Pestell, R. G., Tanowitz, H. B., Sotgia, F., & Lisanti, M. P. (2011) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2011.01.023 · Cited by 248 · see citing works
Glutamine: pleiotropic roles in tumor growth and stress resistance
Shanware, N. P., Mullen, A. R., DeBerardinis, R. J., & Abraham, R. T. (2011) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0731-9 · Cited by 176 · see citing works
Self-citationSun, W. Y., Kim, H. M., Jung, W.-H., & Koo, J. S. (2016) · Journal of Translational Medicine · doi:10.1186/s12967-016-0915-8 · Cited by 77 · see citing works
- Authors
- Eng, C. H., & Abraham, R. T.
- Affiliations
- Pfizer (United States) (US)
- Corresponding author
- Eng, Christina H.
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2010-10
- Volume
- 6
- Issue
- 7
- Pages
- 968-970
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC3039742
- OpenAlex
- W2090212240
- Cited by
- 64
- References
- 1
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 9 · 2022: 2 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 3 · 2015: 7 · 2014: 2 · 2013: 4 · 2012: 8
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Autophagy (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- glutaminolysis, glutamine metabolism, ammonia, mitochondrial metabolism, autophagic flux, autocrine signaling, paracrine signaling, starvation
- MeSH terms
- Ammonia, Autophagy, Glutaminase, Glutamine, Humans, Mitochondria, Culture Media, Conditioned, Cell Line, Tumor
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