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Abstract Phosphatidylinositol 3,5-bisphosphate (PI(3,5)P 2 ) 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)P 2 synthesis increases in response to environmental stimuli, yet how it changes in cycling cells under basal conditions remained elusive. Here, using in vivo biosensors and live cell imaging, we analyzed spatiotemporal changes in PI(3,5)P 2 levels during the cell cycle of the budding yeast S. cerevisiae . We established that PI(3,5)P 2 accumulates on the vacuole in the daughter cell while it disappears from the vacuole in the mother cell during mitosis. Employing a ratiometric in vivo pH sensor, we showed that the daughter vacuole is acidified while the mother vacuole gets alkalinized concomitant with the changes in PI(3,5)P 2 distribution during mitosis. Our results further suggest that the asymmetry of PI(3,5)P 2 and the PI(3,5)P 2 effector Atg18 determine the asymmetry of vacuolar pH, providing insights into how the mother cell ages while the daughter cell is rejuvenated.
Huda et al. (Thu,) studied this question.