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Phosphate‐regulated phosphatases Phm8 and Sdt1 are essential for chronological lifespan in budding yeast

Phosphate (Pi) is an essential and typically limiting nutrient for life. It is therefore critical that acquisition, uptake, storage, utilization and salvage of Pi be highly regulated. In S. cerevisiae, the PHO pathway regulates expression of genes that respond to low environmental Pi. The system includes a cyclin, cyclin‐dependent protein kinase and inhibitor complex, Pho80‐Pho85‐Pho81, the transcriptional activator, Pho4, and a variety of enzymes and targets that have been less well characterized. Here we identify two paralogous metabolite phosphatases, Phm8 and Sdt1, as targets and mediators of the PHO system. We show that Phm8 and Sdt1 are under negative regulation of the Pho80‐Pho85 complex, and are induced transcriptionally by Pho4 under Pi limiting conditions and at stationary phase. Chronological lifespan assays using knock‐out mutants reveal that Phm8 and Sdt1 are required in stationary phase for cells to remain viable and arrest properly in the G1 phase of the cell cycle. These findings define the roles of previously unknown effectors of the PHO system and implicate Pi metabolism as an important factor in chronological lifespan.