HIF-independent role of Prolyl Hydroxylases in the cellular response to amino acids

Duran, R.V., MacKenzie, E.D., Boulahbel, H., Frezza, C., Heiserich, L., Tardito, S. , Rocha, S., Hall, M.N. and Gottlieb, E. (2013) HIF-independent role of Prolyl Hydroxylases in the cellular response to amino acids. Oncogene, 32(38), pp. 4549-4556. (doi: 10.1038/onc.2012.465) (PMID:23085753) (PMCID:PMC3787797)

[img]
Preview
Text
69007.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

1MB

Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tardito, Dr Saverio and Boulahbel, Miss Houda and Heiserich, Ms Lisa and Frezza, Mr Christian and Duran, Dr Raul and Gottlieb, Professor Eyal and MacKenzie, Mrs Elaine
Authors: Duran, R.V., MacKenzie, E.D., Boulahbel, H., Frezza, C., Heiserich, L., Tardito, S., Rocha, S., Hall, M.N., and Gottlieb, E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Oncogene
Publisher:Nature Publishing Group
ISSN:0950-9232
ISSN (Online):1476-5594
Published Online:22 October 2012
Copyright Holders:Copyright © 2013 Macmillan Publishers Limited
First Published:First published in Oncogene 32(38): 4549-4556
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record