When Too Much ATP Is Bad for Protein Synthesis

Abstract Adenosine triphosphate (ATP) is the energy currency of living cells. Even though ATP powers virtually all energy-dependent activities, most cellular ATP is utilized in protein synthesis via tRNA aminoacylation and guanosine triphosphate regeneration. Magnesium (Mg²⁺), the most common divalent cation in living cells, plays crucial roles in protein synthesis by maintaining the structure of ribosomes, participating in the biochemistry of translation initiation and functioning as a counterion for ATP. A non-physiological increase in ATP levels hinders growth in cells experiencing Mg²⁺ limitation because ATP is the most abundant nucleotide triphosphate in the cell, and Mg²⁺ is also required for the stabilization of the cytoplasmic membrane and as a cofactor for essential enzymes. We propose that organisms cope with Mg²⁺ limitation by decreasing ATP levels and ribosome production, thereby reallocating Mg²⁺ to indispensable cellular processes.