Fission yeast cells use distinct cell size control mechanisms for size adaptation to osmotic, oxidative, or low glucose conditions

Abstract

Cells maintain an appropriate size to function, yet the mechanisms that enable size adaptation to environmental stress remain poorly understood. Fission yeast cells enter mitosis and divide at a threshold size when cyclin-dependent kinase (Cdk1) is activated through size- and time-dependent scaling of its regulators: Cdr2 kinase with cell surface area, Cdc25 phosphatase with cell volume, and mitotic cyclin Cdc13 with cell cycle time. This integrated size control network is characterized in nutrient-rich conditions, but under stress it remains unclear which size parameters cells monitor, and which size- or time-sensing pathways mediate adaptation. Using high-throughput image analysis, we quantified the geometry of dividing cells under osmotic, oxidative, and low glucose conditions. Wild-type cells increased their surface area-to-volume (SA:Vol) ratio in low glucose but decreased it under osmotic or oxidative stress, revealing distinct geometric strategies for environmental size adaptation. Genetic perturbations of size- and time-sensing pathways revealed that Cdc25 is required for volume-based adaptation to oxidative and osmotic stress, Cdc13 contributes to osmotic stress response, and Cdr2 promotes surface area-based expansion in low glucose. Although disrupting individual pathways altered normal geometric responses, cells remained viable, suggesting that a modular size control system enables flexible geometric adaptation to changing environments.