Reducing Ribosome Biosynthesis Promotes Translation during Low Mg2+ Stress

The synthesis of ribosomes is regulated by both amino acid abundance and the availability of ATP, which regenerates guanosine triphosphate (GTP), powers ribosomes, and promotes transcription of rRNA genes. We now report that bacteria supersede both of these controls when experiencing low cytosolic magnesium (Mg2+), a divalent cation essential for ribosome stabilization and for neutralization of ATP's negative charge. We uncover a regulatory circuit that responds to low cytosolic Mg2+ by promoting expression of proteins that import Mg2+ and lower ATP amounts. This response reduces the levels of ATP and ribosomes, making Mg2+ ions available for translation. Mutants defective in Mg2+ uptake and unable to reduce ATP levels accumulate nonfunctional ribosomal components and undergo translational arrest. Our findings establish a paradigm whereby cells reduce the amounts of translating ribosomes to carry out protein synthesis.