PI(3,5)P2asymmetry during mitosis is essential for asymmetric vacuolar inheritance

Abstract

AbstractPhosphatidylinositol 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)P2synthesis 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)P2levels during the cell cycle of the budding yeastS. cerevisiae. We established that PI(3,5)P2accumulates 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)P2distribution during mitosis. Our results further suggest that the asymmetry of PI(3,5)P2and the PI(3,5)P2effector Atg18 determine the asymmetry of vacuolar pH, providing insights into how the mother cell ages while the daughter cell is rejuvenated.