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Metabolic Regulation of Hypoxia-Inducible Transcription Factors: The Role of Small Molecule Metabolites and Iron
- Source :
- Biomedicines, Vol 6, Iss 2, p 60 (2018), Biomedicines
- Publication Year :
- 2018
- Publisher :
- MDPI AG, 2018.
-
Abstract
- 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 the 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) and 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 the enzymes involved in chromatin remodelling.
- Subjects :
- 0301 basic medicine
2-OG dependent dioxygenase
PHD
Medicine (miscellaneous)
2-hydroxyglutarate
Review
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
HIF
iron metabolism
lcsh:QH301-705.5
Transcription factor
TCA cycle
chemistry.chemical_classification
hypoxia inducible factors
Chemistry
2-HG
Small molecule
Cell biology
Citric acid cycle
Metabolic pathway
Crosstalk (biology)
030104 developmental biology
Enzyme
lcsh:Biology (General)
Hypoxia-inducible factors
prolyl hydroxylase
Intracellular
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Biomedicines, Vol 6, Iss 2, p 60 (2018), Biomedicines
- Accession number :
- edsair.doi.dedup.....5d67c12519db6ff422d14eb1a4f20763
- Full Text :
- https://doi.org/10.17863/cam.27752