Magnesium and the control of cell proliferation: looking for a needle in a haystack

Experimental evidence supports the important role of magnesium in the process of cellular proliferation, even though cell magnesium homeostasis is not completely clarified. We were the first to describe some molecular characteristics of the magnesium-dependent regulation of the cell cycle, and others proposed a mechanism for the magnesium-dependent regulation of protein synthesis occurring in the early phases of cell proliferation. We will attempt to relate such mechanisms with pathologic conditions whereby cell proliferation is severely disregulated, as in the case of tumors. It is interesting to note that recently some efforts have been made to correlate magnesium transport systems with its functions within the cells. Few, but stimulating new data are emerging which relate molecularly defined ion channels with magnesium homeostasis and its functions. Old and new data are now being merged and corroborated by diverse experimental approaches including molecular genetics, proteomics, electrophysiology and biochemistry. This, together with the development of new techniques to measure cell magnesium content and distribution, will hopefully pave the way to unravel the intimate mechanisms of such an essential though undefined metabolic regulator. New and deeper appreciation of magnesium homeostasis will help in delineating the key role of this cation in the regulation of normal or pathologic cell proliferation.