The signalling lipid PI3,5P 2 is essential for timely mitotic exit

Abstract

Coordination of mitotic exit with chromosome segregation is key for successful mitosis. Mitotic exit in budding yeast is executed by the mitotic exit network (MEN), which is negatively regulated by the spindle position checkpoint (SPOC). SPOC kinase Kin4 is crucial for SPOC activation in response to spindle positioning defects. Here, we report that the lysosomal signalling lipid phosphatidylinositol-3,5-bisphosphate (PI3,5P 2) has an unanticipated role in the timely execution of mitotic exit. We show that the lack of PI3,5P 2 causes a delay in mitotic exit, whereas elevated levels of PI3,5P 2 accelerates mitotic exit in mitotic exit defective cells. Our data indicate that PI3,5P 2 promotes mitotic exit in part through impairment of Kin4. This process is largely dependent on the known PI3,5P 2 effector protein Atg18. Our work thus uncovers a novel link between PI3,5P 2 and mitotic exit. © 2023 Royal Society Publishing. All rights reserved.