Metabolic Regulation of Hypoxia-Inducible Transcription Factors: The Role of Small Molecule Metabolites and Iron.
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Bailey, P., & Nathan, J. (2018). Metabolic Regulation of Hypoxia-Inducible Transcription Factors: The Role of Small Molecule Metabolites and Iron.. Biomedicines, 6 (2)https://doi.org/10.3390/biomedicines6020060
Hypoxia-inducible transcription factors (HIFs) facilitate cellular adaptations to low-oxygen environments. However, it is increasingly recognised that HIFs may be activated in response to metabolic stimuli, even when oxygen is present. Understanding the mechanisms for the crosstalk that exists between HIF signalling and metabolic pathways is therefore important. This review focuses on this metabolic regulation of HIFs by small molecule metabolites and iron, highlighting the latest studies that explore how Tricarboxylic Acid (TCA) cycle intermediates, 2-hydroxyglutarate (2-HG) or intracellular iron levels influence the HIF response through modulating the activity of prolyl hydroxylases (PHDs). We also discuss the relevance of these metabolic pathways in physiological and disease contexts. Lastly, as PHDs are members of a large family of 2-oxoglutarate (2-OG) dependent dioxygenases that can all respond to metabolic stimuli, we explore the broader role of TCA cycle metabolites and 2-HG in the regulation of 2-OG dependent dioxygenases, focusing on those enzymes involved in chromatin remodelling.
Wellcome Trust (102770/Z/13/Z)
Lister Institute of Preventive Medicine (unknown)
Wellcome Trust (100140/Z/12/Z)
Wellcome Trust (205252/Z/16/Z)
External DOI: https://doi.org/10.3390/biomedicines6020060
This record's URL: https://www.repository.cam.ac.uk/handle/1810/280381
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/