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 Mg2+ homeostasis and transport still remains incomplete. For example, the occurrence of major fluxes of Mg2+ 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 Mg2+ homeostasis and how these mechanisms are altered under specific pathological conditions.

SLC41A1, a Na+/Mg2+ exchanger, is downregulated during exercise

“…Thus, we hypothesize that a downregulated SLC41A1 gene by means of non-exercise or Mg supplementation leads to an increase of Mg in the blood that could confer benefits similar to those observed with exercise, as consumption of various Mg supplements by Mg-deficient subjects is known to have beneficial effects (1)(2)(3)(4). Mg is also widely used in the treatment of diseases, including but not limited to, asthma, heart disease, blood clots, hypertension, osteoporosis and hypoglycemia.…”

“…However, the factors that facilitate Mg transportation also do not rely solely on the SLC41A1 gene, and there are at least nine Mg-sensitive genes (CNNM2, TRPM6, TRPM7, N33, SLC41A1, SLC41A2, SLC41A3, MagT1 and NIPA1) that have been shown to be involved in manipulating intra-and extracellular Mg transportation (2). In the present study, the SLC41A1 gene was downregulated, resulting in an increase and then decrease of Mg levels in the blood during the treadmill exercise.…”

“…Homeostatic serum or plasma Mg concentrations are closely controlled and maintained, ensuring the appropriate activities for metabolism, neuronal excitability and muscle contraction through a variety of Mg transporters and ionic channels (2). Numerous Mg-sensitive genes, based on molecular and functional characterizations, are responsible for this homeostatic mechanism.…”

“…Numerous Mg-sensitive genes, based on molecular and functional characterizations, are responsible for this homeostatic mechanism. In addition, Mg-sensitive gene expression has been demonstrated to markedly fluctuate during physiological and pathological events (2,3). However, the mechanism responsible for regulating plasma Mg concentrations remains to be determined.…”

A Rationally Designed, Spiropyran-Based Chemosensor for Magnesium

“…Magnesium ions (Mg 2+ ) play an important role in mammalian cell function [1][2][3][4], as an enzymatic cofactor [5], regulator of cellular ion channels [6][7][8] and energy metabolism [9]. Conditions such as Type 2 Diabetes [10][11][12], Alzheimer's [13,14] and cardiovascular disease [15,16] have been linked with magnesium deficiency, however the mechanisms of Mg 2+ regulation in such disease states are poorly understood [17,18].…”