Iron regulatory factor--the conductor of cellular iron regulation

Blood Rev. 1993 Dec;7(4):251-8. doi: 10.1016/0268-960x(93)90012-s.

Abstract

All cells have to adjust uptake, utilization and storage of iron according to the availability and their requirement for this essential metal. Progress in recent years has led to the elucidation of the molecular control mechanisms that co-ordinate the uptake, utilization and storage of iron in mammalian cells and has highlighted the role of a newly-identified regulatory protein, the iron regulatory factor (IRF). IRF is a cytoplasmic protein that senses the intracellular iron level and responds by adjusting its function. When the iron level is low, it binds to so-called 'iron responsive elements' (IREs) contained in the mRNAs encoding proteins involved in iron metabolism and erythroid haem synthesis. When levels of cellular iron rise, IRF converts into the enzyme aconitase and looses its ability to bind to IREs. We discuss both functions of this Janus face protein and describe how its function is controlled by the status of an iron sulphur cluster in the IRF protein. We also speculate about how an IRF-mediated regulation may relate to certain medical disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aconitate Hydratase / physiology*
  • Animals
  • Biological Transport
  • Citrates / metabolism
  • Citric Acid
  • Gene Expression Regulation
  • Heme / metabolism
  • Hemochromatosis / metabolism
  • Humans
  • Iron / metabolism*
  • Iron-Regulatory Proteins
  • Mammals / metabolism
  • Protein Biosynthesis
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / physiology*
  • Receptors, Transferrin / metabolism

Substances

  • Citrates
  • Iron-Regulatory Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Receptors, Transferrin
  • Citric Acid
  • Heme
  • Iron
  • Aconitate Hydratase