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Type: Journal article
Title: The Factor Inhibiting HIF asparaginyl hydroxylase regulates oxidative metabolism and accelerates metabolic adaptation to hypoxia
Author: Sim, J.
Cowburn, A.
Palazon, A.
Madhu, B.
Tyrakis, P.
Macias, D.
Bargiela, D.
Pietsch, S.
Gralla, M.
Evans, C.
Kittipassorn, T.
Chey, Y.
Branco, C.
Rundqvist, H.
Peet, D.
Johnson, R.
Citation: Cell Metabolism, 2018; 27(4):898-e.7
Publisher: Elsevier (Cell Press)
Issue Date: 2018
ISSN: 1550-4131
Statement of
Jingwei Sim, Andrew S. Cowburn, Asis Palazon, Basetti Madhu, Petros A. Tyrakis, David Macı, as, David M. Bargiela, Sandra Pietsch, Michael Gralla, Colin E. Evans, Thaksaon Kittipassorn, Yu C.J. Chey, Cristina M. Branco, Helene Rundqvist, Daniel J. Peet, and Randall S. Johnson
Abstract: Animals require an immediate response to oxygen availability to allow rapid shifts between oxidative and glycolytic metabolism. These metabolic shifts are highly regulated by the HIF transcription factor. The Factor Inhibiting HIF (FIH) is an asparaginyl hydroxylase that controls HIF transcriptional activity in an oxygen-dependent manner. We show here that FIH loss increases oxidative metabolism, while also increasing glycolytic capacity, and that this gives rise to an increase in oxygen consumption. We further show that the loss of FIH acts to accelerate the cellular metabolic response to hypoxia. Skeletal muscle expresses 50-fold higher levels of FIH than other tissues: we analyzed skeletal muscle FIH mutants, and found a decreased metabolic efficiency, correlated with an increased oxidative rate and an increased rate of hypoxic response. We find that FIH, through its regulation of oxidation, acts in concert with the PHD/VHL pathway to accelerate HIF-mediated metabolic responses to hypoxia.
Keywords: Animals; Mice, Inbred C57BL; Mice; Oxygen; Mixed Function Oxygenases; Procollagen-Proline Dioxygenase; Adaptation, Physiological; Signal Transduction; Cell Hypoxia; Transcription, Genetic; Gene Expression Regulation; Glycolysis; Oxygen Consumption; Male; Von Hippel-Lindau Tumor Suppressor Protein; Hypoxia-Inducible Factor-Proline Dioxygenases
Description: Published: April 3, 2018
Rights: © 2018 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (
RMID: 0030084715
DOI: 10.1016/j.cmet.2018.02.020
Appears in Collections:Molecular and Biomedical Science publications

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