Abstract
Simple SummaryInorganic polyphosphate, a linear polymer of orthophosphoric acid, plays an important role in microorganisms’ stress resistance. Vtc4 protein synthetizes inorganic polyphosphate in yeast. Here we show that yeast lacking this protein exhibit very low polyphosphate level, decreased resistance to alkaline stress, but increased resistance to oxidative and heavy metal stresses. We suggest the increased stress resistance is achieved by constitutive up-regulation of oxidative stress-response genes and decreased expression of Pho84 that is responsible for manganese uptake.Inorganic polyphosphate (polyP) is an important factor of alkaline, heavy metal, and oxidative stress resistance in microbial cells. In yeast, polyP is synthesized by Vtc4, a subunit of the vacuole transporter chaperone complex. Here, we report reduced but reliably detectable amounts of acid-soluble and acid-insoluble polyPs in the Δvtc4 strain of Saccharomyces cerevisiae, reaching 10% and 20% of the respective levels of the wild-type strain. The Δvtc4 strain has decreased resistance to alkaline stress but, unexpectedly, increased resistance to oxidation and heavy metal excess. We suggest that increased resistance is achieved through elevated expression of DDR2, which is implicated in stress response, and reduced expression of PHO84 encoding a phosphate and divalent metal transporter. The decreased Mg2+-dependent phosphate accumulation in Δvtc4 cells is consistent with reduced expression of PHO84. We discuss a possible role that polyP level plays in cellular signaling of stress response mobilization in yeast.
Highlights
Yeast genomes do not contain orthologs of bacterial polyphosphate kinases, and polyP synthesis is performed by the Vtc4 protein [17]
The search for homologues of Vacuole Transporter Chaperone (VTC) complex proteins in fungi revealed that the complex is ancient and at least one component (Vtc4, but likely Vtc1) was present early in the evolutionary history of fungi, while Vtc2 and Vtc3 result from a recent duplication in the S. cerevisiae lineage [21]
PolyPs in polyP1, polyP2, and polyP3 fractions were hydrolyzed by Ppx1 polyphosphatase; in both strains, the hydrolysis was incomplete (Figure 1A)
Summary
PolyP and enzymes of its metabolism are involved in various processes regulating vital activities of the cell. PolyPs are important for stress response and virulence [1,5,6], whereas, in the human organism, polyPs play is involved in bone tissue growth and development [7,8], blood coagulation cascade, inflammatory response [9], and signal transduction in astrocytes [10]. PolyP is a component of a specific calcium channel in mitochondrial membranes regulating calcium level and stress response [11]. PolyPs are involved in the control of the cell cycle [12], stress response [13,14,15], and virulence [16]. The search for homologues of VTC complex proteins in fungi revealed that the complex is ancient and at least one component (Vtc, but likely Vtc1) was present early in the evolutionary history of fungi, while Vtc and Vtc result from a recent duplication in the S. cerevisiae lineage [21]
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