Cellular magnesium homeostasis

Abstract

Magnesium, the second most abundant cellular cation after potassium, is essential to regulate numerous cellular functions and enzymes, including ion channels, metabolic cycles, and signaling pathways, as attested by more than 1000 entries in the literature. Despite significant recent progress, however, our understanding of how cells regulate Mg(2+) homeostasis and transport still remains incomplete. For example, the occurrence of major fluxes of Mg(2+) in either direction across the plasma membrane of mammalian cells following metabolic or hormonal stimuli has been extensively documented. Yet, the mechanisms ultimately responsible for magnesium extrusion across the cell membrane have not been cloned. Even less is known about the regulation in cellular organelles. The present review is aimed at providing the reader with a comprehensive and up-to-date understanding of the mechanisms enacted by eukaryotic cells to regulate cellular Mg(2+) homeostasis and how these mechanisms are altered under specific pathological conditions.

Figure 1. Regulation of cellular Mg²⁺ homeostasis

The cartoon summarizes the principal mechanisms controlling cellular Mg²⁺ homeostasis, compartmentation, and transport in and out of mammalian cell, as well as the main cellular functions regulated by changes in Mg²⁺ content within different compartments. For mere practical purpose, the entry mechanisms have been assigned to the apical domain of the cell. Abbreviation used in the figure: ER = endoplasmic reticulum; G6Pase = glucose 6 phosphatase; Mito = mitochondria; β-AR = β-adrenergic receptor; AC = adenylyl cyclase; NMx = Na⁺/Mg²⁺ exchanger; Me²⁺ = divalent cations; VP-R = vasopressin receptor; PMA = Phorbol-Myristate Acetate; PKC = Protein Kinase C.