Metabolic consequences of polyphosphate synthesis and imminent phosphate limitation

Abstract

Cells stabilize intracellular inorganic phosphate (Pi) to compromise between large biosynthetic needs and detrimental bioenergetic effects of Pi. Pihomeostasis in eukaryotes employs SPXs domains, which are receptors for inositol pyrophosphates. We explored how polymerization and storage of Pi in acidocalcisome-like vacuoles supports S. cerevisiae metabolism and how these cells recognize Piscarcity. Whereas Pistarvation affects numerous metabolic pathways, beginning Piscarcity affects few metabolites. These include inositol pyrophosphates and ATP, a low-affinity substrate for inositol pyrophosphate-synthesizing kinases. Declining ATP and inositol pyrophosphates may thus be indicators of impending Pilimitation. Actual Pistarvation triggers accumulation of the purine synthesis intermediate 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), which activates Pi-dependent transcription factors. Cells lacking polyphosphate show Pistarvation features already under Pi-replete conditions, suggesting that vacuolar polyphosphate supplies Pifor metabolism even when Piis abundant. However, polyphosphate deficiency also generates unique metabolic changes that are not observed in starving wildtype cells. Polyphosphate in acidocalcisome-like vacuoles may hence be more than a global phosphate reserve and channel Pito preferred cellular processes.

Promoting Nucleic Acid Synthesis in Saccharomyces cerevisiae through Enhanced Expression of Rrn7p, Rrn11p, IMPDH, and Pho84p

“…42−44 In addition, Kim et al reported that phosphate starvation led to reduced accumulation of phosphate-containing nucleotides, nucleoside diphosphates, and nucleoside triphosphates. 45 The results of this study confirm this point. Therefore, increasing the availability of phosphate through supplementation of the fermentation medium and stimulating uptake through phosphate transporters in the HNAC mutant strain can be an effective strategy for enhancing RNA production.…”

Dysregulating PHO Signaling via the CDK Machinery Differentially Impacts Energy Metabolism, Calcineurin Signaling, and Virulence in Cryptococcus neoformans

“…In support of our findings, it has recently been reported that S. cerevisiae lacking polyP shows P i starvation features already under P i − -replete conditions. Based on their metabolomics studies, the authors concluded that vacuolar polyP supplies P i for metabolism even when P i is abundant ( 57 ). A reciprocal relationship between ATP and polyP in eukaryotic cells, and a regulatory connection between their relative abundance and synthesis affecting cellular phosphate homeostasis and primary metabolism, have also been reported by others ( 58 ).…”