HIF-independent role of prolyl hydroxylases in the cellular response to amino acids

Durán, R. V. and Mackenzie, E. D. and Boulahbel, H. and Frezza, C. and Heiserich, L. and Tardito, S. and Bussolati, O. and Rocha, S. and Hall, M. N. and Gottlieb, E.. (2012) HIF-independent role of prolyl hydroxylases in the cellular response to amino acids. Oncogene, 32 (38). pp. 4549-4556.

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Hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs) are α-ketoglutarate (αKG)-dependent dioxygenases that function as cellular oxygen sensors. However, PHD activity also depends on factors other than oxygen, especially αKG, a key metabolic compound closely linked to amino-acid metabolism. We examined the connection between amino-acid availability and PHD activity. We found that amino-acid starvation leads to αKG depletion and to PHD inactivation but not to HIF stabilization. Furthermore, pharmacologic or genetic inhibition of PHDs induced autophagy and prevented mammalian target of rapamycin complex 1 (mTORC1) activation by amino acids in a HIF-independent manner. Therefore, PHDs sense not only oxygen but also respond to amino acids, constituting a broad intracellular nutrient-sensing network.Oncogene advance online publication, 22 October 2012; doi:10.1038/onc.2012.465.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
UniBasel Contributors:Hall, Michael N.
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:05 Oct 2017 10:09
Deposited On:01 Feb 2013 08:41

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