MetalloregulationBased in part on the article Metalloregulation by Robert P. Hausinger which appeared in theEncyclopedia of Inorganic Chemistry, First Edition.

Abstract

Metalloregulation refers to the concept that living organisms from bacteria to mammals must orchestrate the processes of metal import, utilization, sequestration, and export to optimize availability of metals for use in metabolism. Metals are required for the function of many proteins, but metals can also be toxic because free metal ions may react with protein, nucleic acid, and lipid contents of cells. In general, metals are transported across membranes by specific unidirectional transporters, and cells and organisms regulate the abundance of specific transporters and metal sequestration proteins to meet their needs. Changes in abundance result mainly from changes in either the rate of transcription, the stability of mRNA, the translation rate, or the stability of the metal protein. Complex regulatory frameworks exist to govern metal homeostasis in virtually all cells and organisms. Usually a central component of a successful regulatory network is a protein that registers metal availability by directly binding the metal ion that requires regulation. Metal binding then drives a change in function of the central regulatory protein, which usually has multiple regulatory targets that include transporters, chaperone proteins, sequestration molecules, and others. In this chapter, we focus on the main regulatory proteins of iron homeostasis in bacteria, yeast, plants, and mammals, and those involved with regulation of zinc homeostasis in bacteria and yeast. We describe the sensing mechanism and targets of the bacterial transcription factor, fur, and the yeast transcription factors known as Aft 1 and 2. In mammals, we focus on the sensing and regulatory mechanisms utilized by iron regulatory proteins (IRPs) and on the role of the peptide hormone hepcidin in physiologic regulation of iron metabolism. In zinc homeostasis, we focus on the bacterial transcription factors Zur and Znt 1, and the yeast transcription factor, Zap1. References for regulation of copper, manganese, and nickel metabolism are cited for further reading. Nature has produced a wide variety of solutions to the important question of how cells and organisms can ‘sense’ their metal status and modify gene expression to ensure that metals are appropriately available for use in metabolism.