PI(3,5)P 2 asymmetry during mitosis is essential for asymmetric vacuolar inheritance

Phosphatidylinositol 3,5-bisphosphate (PI(3,5)P₂) is a low-abundance signaling lipid that plays crucial roles in various cellular processes, including endolysosomal system structure/function, stress response, and cell cycle regulation. PI(3,5)P₂ synthesis increases in response to environmental stimuli, yet its behavior in cycling cells under basal conditions remains elusive. Here, we analyzed spatiotemporal changes in PI(3,5)P₂ levels during the cell cycle of S. cerevisiae. We found that PI(3,5)P₂ accumulates on the vacuole in the daughter cell while it disappears from the vacuole in the mother cell during mitosis. Concomitant with the changes in PI(3,5)P₂ distribution, the daughter vacuole became more acidic, whereas the acidity of the mother vacuole decreased during mitosis. Our data further showed that both PI(3,5)P₂ and the PI(3,5)P₂ effector protein Atg18 are determinants of vacuolar-pH asymmetry and acidity. Our work, thus, identifies PI(3,5)P₂ as a key factor for the establishment of vacuolar-pH asymmetry, providing insights into how the mother cell ages while the daughter cell is rejuvenated.

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