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New perspectives on the molecular basis of the interaction between oxygen homeostasis and iron metabolism

Authors Recalcati S, Gammella E, Cairo G

Received 31 July 2015

Accepted for publication 5 November 2015

Published 11 December 2015 Volume 2015:3 Pages 93—103

DOI https://doi.org/10.2147/HP.S83537

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Prof. Dr. Max Gassmann

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Dörthe Katschinski


Stefania Recalcati, Elena Gammella, Gaetano Cairo

Department of Biomedical Sciences for Health, University of Milan, Milan, Italy

Abstract: Oxygen and iron are two elements closely related from a (bio)chemical point of view. Moreover, they share the characteristic of being indispensable for life, while also being potentially toxic. Therefore, their level is strictly monitored, and sophisticated pathways have evolved to face variations in either element. In addition, the expression of proteins involved in iron and oxygen metabolism is mainly controlled by a complex interplay of proteins that sense both iron levels and oxygen availability (ie, prolyl hydroxylases, hypoxia inducible factors, and iron regulatory proteins), and in turn activate feedback mechanisms to re-establish homeostasis. In this review, we describe how cells and organisms utilize these intricate networks to regulate responses to changes in oxygen and iron levels. We also explore the role of these pathways in some pathophysiological settings.

Keywords: hypoxia, prolyl hydroxylases, hypoxia inducible factors, iron regulatory proteins, proteasome

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