Phosphate Starvation by Energy Metabolism Disturbance in Δ/Δ Induces Lipid Droplet Accumulation and Cell Membrane Damage.

Phosphorus in the form of phosphate (Pi) is an essential element for metabolic processes, including lipid metabolism. In yeast, the inositol polyphosphate kinase mediated synthesis of inositol heptakisphosphate (IP) regulates the phosphate-responsive (PHO) signaling pathway, which plays an important role in response to Pi stress. The role of in Pi stress and lipid metabolism of has not yet been studied. We found that when Δ/Δ was grown in glucose medium, if Pi was supplemented in the medium or mitochondrial Pi transporter was overexpressed in the strain, the lipid droplet (LD) content was reduced and membrane damage was alleviated. However, further studies showed that neither the addition of Pi nor the overexpression of the Pi transporter affected the energy balance of Δ/Δ. In addition, the LD content of Δ/Δ grown in Pi limitation medium PNMC was lower than that grown in SC, and the metabolic activity of Δ/Δ grown in PNMC was also lower than that grown in SC medium. This suggests that the increase in Pi demand by a high energy metabolic rate is the cause of LD accumulation in Δ/Δ. In addition, in the Δ/Δ strains, the core transcription factor in the PHO pathway was transported to the vacuole and degraded, which reduced the pathway activity. However, this does not mean that knocking out completely blocks the activation of the PHO pathway, because the LD content of Δ/Δ grown in the medium with β-glycerol phosphate as the Pi source was significantly reduced. In summary, the increased Pi demand and the decreased PHO pathway activity in Δ/Δ ultimately lead to LD accumulation and cell membrane damage.