Cellular Adaptations to Cytoplasmic Mg²⁺ Limitation

Mg²⁺ is the most abundant divalent cation in living cells. It is essential for charge neutralization, macromolecule stabilization, and the assembly and activity of ribosomes and as a cofactor for enzymatic reactions. When experiencing low cytoplasmic Mg²⁺, bacteria adopt two main strategies: They increase the abundance and activity of Mg²⁺ importers and decrease the abundance of Mg²⁺-chelating ATP and rRNA. These changes reduce regulated proteolysis by ATP-dependent proteases and protein synthesis in a systemic fashion. In many bacterial species, the transcriptional regulator PhoP controls expression of proteins mediating these changes. The 5' leader region of some mRNAs responds to low cytoplasmic Mg²⁺ or to disruptions in translation of open reading frames in the leader regions by furthering expression of the associated coding regions, which specify proteins mediating survival when the cytoplasmic Mg²⁺ concentration is low. Microbial species often utilize similar adaptation strategies to cope with low cytoplasmic Mg²⁺ despite relying on different genes to do so.