Overexpression of polyphosphate polymerases and deletion of polyphosphate phosphatases shorten the replicative lifespan in yeast

Abstract

We previously found that overexpression of phosphate starvation‐responsive genes by disrupting PHO80 led to a shortened replicative lifespan in yeast. To identify lifespan‐related genes, we screened upregulated genes in the pho80Δ mutant and focused on the VTC genes, which encode the vacuolar polyphosphate (polyP) polymerase complex. VTC1/VTC2/VTC4 deletion restored the lifespan and intracellular polyP levels in pho80Δ. In the wild type, overexpression of VTC5 or a combination of the other VTCs caused high polyP accumulation and shortened lifespan. Similar phenotypes were caused by the deletion of polyP phosphatase genes—vacuolar PPN1 and cytosolic PPX1. The polyP‐accumulating strains exhibited stress sensitivities. Thus, we demonstrated that polyP metabolic enzymes participate in replicative lifespan, and extreme polyP accumulation shortens the lifespan.