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Novel mechanisms for regulating polyphosphate metabolism in Saccharomyces cerevisiae
To ensure a continuous supply of phosphate, living organisms have devised complex mechanisms to regulate the uptake and subsequent utilization of this essential nutrient. An important aspect of phosphate metabolism is the storage of excess phosphate as the polymer, polyphosphate. Despite the importance of this polymer to all living organisms, much needs to be learned about its synthesis, storage, or utilization. Furthermore, little is known about the regulatory mechanisms that determine when polyphosphate synthesis or degradation is appropriate. Our work has shown that polyphosphate is a dynamic molecule whose levels fluctuate during the cell cycle. Polyphosphate levels are high in G1, and subsequently drop as the cell uses free phosphate during cell division. Mitotic induction of phosphate regulatory genes, including the acid phosphatase gene PHO5, replenishes polyphosphate levels late in the mitosis. Furthermore, we have shown that Mcm1 and Fkh1, two cell cycle dependent transcriptional activators, contribute to mitotic activation of PHO5. In addition, we have elucidated the importance of regulating polyphosphate synthesis. Strains lacking the cyclin Pho80 have increased expression of the polyphosphate synthase genes, PHM1-4, and thus have highly elevated polyphosphate levels. Hyperaccumulation of polyphosphate results in severe growth defects on medium containing high levels of sorbitol, presumably through the polyphosphate-dependent overacidification of the vacuole.
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