Protein synthesis controls phosphate homeostasis

Abstract

Phosphorus is an essential element assimilated largely as orthophosphate (Pi). Cells respond to Pi starvation by importing Pi from their surroundings. We now report that impaired protein synthesis alone triggers a Pi starvation response even when Pi is plentiful in the extracellular milieu. In the bacterium serovar Typhimurium this response entails phosphorylation of the regulatory protein PhoB and transcription of PhoB-dependent Pi transporter genes and is eliminated upon stimulation of adenosine triphosphate (ATP) hydrolysis. When protein synthesis is impaired due to low cytoplasmic magnesium (Mg), triggers the Pi starvation response because ribosomes are destabilized, which reduces ATP consumption and thus free cytoplasmic Pi. This response is transient because low cytoplasmic Mg promotes an uptake in Mg and a decrease in ATP levels, which stabilizes ribosomes, resulting in ATP consumption and Pi increase, thus ending the response. Notably, pharmacological inhibition of protein synthesis also elicited a Pi starvation response in the bacterium and the yeast Our findings identify a regulatory connection between protein synthesis and Pi homeostasis that is widespread in nature.

The small protein MgtS and small RNA MgrR modulate the PitA phosphate symporter to boost intracellular magnesium levels

“…We do not know the mechanisms by which MgtS and PitA impact PhoRB activity. Interestingly, low Mg 2+ was recently found to activate the PhoRB response in S. enterica due to low free cytoplasmic phosphate levels brought about by decreased protein synthesis associated with reduced ATP consumption, though induction of the reporter construct was only observed after 120 min (Pontes and Groisman, ). Independent of the mechanisms, we followed up our observation that MgtS acts through PitA to test the effect of different MgtS alleles and explore the consequences for growth on low Mg 2+ .…”

“…PhoR is converted to its kinase state, thereby mimicking low phosphate conditions and resulting in the activation of the PhoRB regulon. Consistent with this, it was recently found that low intracellular Mg 2+ in Salmonella enterica strains lacking Mg 2+ transporters led to induction of the PhoRB regulon (Pontes and Groisman, ). It also is interesting to note that mutations in pitA , mgrB and phoQ all were found in screens for long‐term adaptation to the antibiotic trimethoprim in LB medium (Baym et al ., ).…”

“…These seemingly conflicting results could be explained by differences between the effects of MgtS overexpression in LB medium versus chromosomally expressed MgtS in N minimal medium with limited Mg 2+ as well as incomplete understanding of PhoRB activation. Indeed, there are conflicting reports of whether PhoRB detects extracellular phosphate at the periplasm (Hsieh and Wanner, ) or intracellular phosphate at the cytoplasm (Pontes and Groisman, ). Regardless, our observations that two Mg 2+ ‐responsive small gene products can promote intracellular Mg 2+ accumulation by modulating the PitA phosphate symporter adds yet another area of regulatory crosstalk between Mg 2+ and phosphate homeostasis.…”

No wisdom in the crowd: genome annotation in the era of big data – current status and future prospects

“…Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology, Microbial Biotechnology, 11, 588-605 phosphate uptake by the Pst system (Brokaw et al, 2017). Interestingly, impairing translation triggers a phosphate starvation response (Pontes and Groisman, 2018). A plausible conjecture is therefore that PhoU is an enzyme, producing yet another metabolite, presumably containing phosphate, that interferes with homeostasis of phosphate metabolism associated with the ATP control of translation, perhaps via translation throttle EttA (Boel et al, 2014).…”

Limitation of phosphate assimilation maintains cytoplasmic magnesium homeostasis

“…This process reduces electrostatic repulsion among Pi groups in the rRNA backbone, enabling the folding and assembly of functional ribosomes. Not accidentally, ATP and rRNA constitute the largest cytoplasmic reservoirs of Pi and Mg 2+ (9,11,(13)(14)(15)(16)(17)(18). Given this inherent connection between Pi and Mg 2+ , we wondered if cytotoxic effects of excessive Pi uptake result from its assimilation into ATP and subsequent disruption of Mg 2+ dependent processes in the cytoplasm.…”