biostudies-literatureUnknownKang PJNIA NIH HHSThe small GTPase Cdc42 is a central regulator of cell polarity, but it is often hyperactivated in aged cells, contributing to senescence and aging in both yeast and animal cells. Yet, the mechanisms underlying its age-related upregulation remain poorly understood. Here, we examine how Cdc42 levels change over successive divisions in budding yeast, which undergoes asymmetric cell division, leading to aging predominantly in mother cells. Using microfluidics-based live-cell imaging and genetic analyses, we find that Cdc42 protein is unevenly distributed between mother and daughter cells during division. Notably, daughter cells inherit lower levels of Cdc42, which helps them rejuvenate. This asymmetry depends on Cdc42's association with endomembranes and requires the presence of farnesylated YbioRxiv : the preprint server for biology2025.07.10.664052https://www.ebi.ac.uk/biostudies/studies/S-EPMC12265609biostudies-literatureCdc42 Partitioning by Chaperone Ydj1 During Asymmetric Division and Aging in Yeast.PMC12265609R21 AG060028Mazak HLee SSKang PJPark HOfalseCdc42 Partitioning by Chaperone Ydj1 During Asymmetric Division and Aging in Yeast.The small GTPase Cdc42 is a central regulator of cell polarity, but it is often hyperactivated in aged cells, contributing to senescence and aging in both yeast and animal cells. Yet, the mechanisms underlying its age-related upregulation remain poorly understood. Here, we examine how Cdc42 levels change over successive divisions in budding yeast, which undergoes asymmetric cell division, leading to aging predominantly in mother cells. Using microfluidics-based live-cell imaging and genetic analyses, we find that Cdc42 protein is unevenly distributed between mother and daughter cells during division. Notably, daughter cells inherit lower levels of Cdc42, which helps them rejuvenate. This asymmetry depends on Cdc42's association with endomembranes and requires the presence of farnesylated Y2025-01-01T00:00:00Z2025 Jul2026-07-09T13:10:33.827Z2025-08-14T03:05:51.672ZS-EPMC122656094067229910.1101/2025.07.10.664052