Hormonal regulation of Mg2+ transport and homeostasis in eukaryotic cells.

Abstract

The high concentrations of total and free magnesium (Mg2+ f ) within eukaryotic cells and its role as an essential co-factor or regulator for numerous cellular enzymes and functions surprisingly contrasts with the minimal knowledge of the mechanisms, genes and proteins that regulate Mg2+ homeostasis at the cellular and organismal level. The reasons for this limited knowledge are both conceptual and methodological. Conceptually, the abundance of intracellular Mg2+ has led to the idea that no major changes in Mg2+ concentration occur or are required, as the cation is plentiful at all times for its co-factor role. It is therefore unlikely to operate as a ‘on-off switch’ for enzymes inside the cell as Ca2+ and other second messengers do. In turn, this point of view has limited interest in developing suitable techniques and methodological approaches to measure changes in cellular Mg2+ concentration accurately. In the last 25 years, however, the concept that the intracellular content and/or concentration of Mg2+ is static has been revisited based on an increasing number of reports indicating that total cellular and plasma Mg2+ content can change significantly following varying hormonal and non-hormonal stimuli and consequently have a major physiological and/or pharmacological role in modulating cell and tissue functions. At the same time, to better detect changes in cellular Mg2+ concentration, technical approaches have been improved or developed. Although not all of them may work in every eukaryotic cell or tissue, we are now better equipped to detect and measure variations in cellular Mg2+ homeostasis and distribution. The present review will attempt to provide a general framework to understand how cellular Mg2+ content and transport are regulated in eukaryotic cells, and how changes in cellular and plasma Mg2+ content contribute to a physiological regulation of intracellular and extracellular enzymes. We will emphasize mammalian cells since Mg2+ transport in Arabidopsis is reviewed by Shaul in this issue. In addition, Mg2+ homeostasis in the kidney is reviewed by Romero.