Regulators of Iron Homeostasis: New Players in Metabolism, Cell Death, and Disease

Trends Biochem Sci. 2016 Mar;41(3):274-286. doi: 10.1016/j.tibs.2015.11.012. Epub 2015 Dec 23.


Iron is necessary for life, but can also cause cell death. Accordingly, cells evolved a robust, tightly regulated suite of genes for maintaining iron homeostasis. Previous mechanistic studies on iron homeostasis have granted insight into the role of iron in human health and disease. We highlight new regulators of iron metabolism, including iron-trafficking proteins [solute carrier family 39, SLC39, also known as ZRT/IRT-like protein, ZIP; and poly-(rC)-binding protein, PCBP] and a cargo receptor (NCOA4) that is crucial for release of ferritin-bound iron. We also discuss emerging roles of iron in apoptosis and a novel iron-dependent cell death pathway termed 'ferroptosis', the dysregulation of iron metabolism in human pathologies, and the use of iron chelators in cancer therapy.

Keywords: NCOA4; SLC39; ferritin; ferroportin; ferroptosis; iron chelator.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cell Death*
  • Homeostasis*
  • Humans
  • Iron / metabolism*


  • Iron