Vtc5, a novel subunit of the vacuolar transporter chaperone complex, regulates polyphosphate synthesis and phosphate homeostasis in yeast.

SPX domains control phosphate homeostasis in eukaryotes. Ten genes in yeast encode SPX-containing proteins, among which YDR089W is the only one of unknown function. Here, we show that YDR089W encodes a novel subunit of the Vacuole Transporter Chaperone (VTC) complex that produces inorganic polyphosphate (polyP). PolyP synthesis transfers inorganic phosphate (Pi) from the cytosol into the acidocalcisome- and lysosome-related vacuoles of yeast, from where it can be released again. It was hence proposed to buffer changes in cytosolic Pi concentration (1). Vtc5 physically interacts with the VTC complex and accelerates the accumulation of polyP synthesized by it go to this site. Deletion of VTC5 reduces polyP accumulation in vivo and in vitro. Its overexpression hyper-activates polyP production and triggers the phosphate starvation response via the PHO pathway. Since this Vtc5-induced starvation response can be reverted by shutting down polyP synthesis genetically or pharmacologically, we propose that polyP synthesis rather than Vtc5 itself is a regulator of the PHO pathway. Our observations suggest that polyP synthesis not only serves to establish a buffer for transient drops in cytosolic Pi levels, but that it can actively decrease or increase the steady state of cytosolic Pi.