Wang Shixing, Kailash Deepthi, Mukherji Shankar
Department of Physics, Washington University in St. Louis, St. Louis, MO, USA.
Department of Physics, Washington University in St. Louis, St. Louis, MO, USA; Department of Cell Biology & Physiology, Washington University School of Medicine, St. Louis, MO, USA; Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO, USA.
Cell Syst. 2025 Jun 18;16(6):101267. doi: 10.1016/j.cels.2025.101267. Epub 2025 Jun 6.
A complete framework of eukaryotic cellular growth control must include the growth of its defining hallmarks: organelles. Organelle coordination with cellular growth is opaque without measuring multiple organelles in the same cell with adequate statistics to test theoretical frameworks. Here, we map out the correlation structure of systems-level organelle biogenesis with cellular growth using "rainbow yeast," simultaneously visualizing 6 major metabolically active organelles. Hyperspectral imaging of thousands of rainbow yeast cells revealed that systems-level organelle biogenesis is organized into collective organelle modes activated by changes in nutrient availability. Chemical biological dissection suggests that sensed growth rate and cell size specifically activate these organelle modes. Mathematical modeling and synthetic control of cytoplasmic availability suggest that the organelle mode structure allows growth homeostasis in constant environments and responsiveness to environmental change. This regulatory architecture may underlie how compartmentalization allows cell size and growth rate flexibility to satisfy otherwise incompatible environmental and developmental constraints.
一个完整的真核细胞生长控制框架必须包括其标志性特征（细胞器）的生长。如果没有在同一细胞中对多个细胞器进行测量，并具备足够的统计数据来检验理论框架，细胞器与细胞生长之间的协调性就难以理解。在此，我们利用“彩虹酵母”描绘了系统水平的细胞器生物发生与细胞生长之间的相关结构，同时可视化6种主要的代谢活跃细胞器。对数千个彩虹酵母细胞的高光谱成像显示，系统水平的细胞器生物发生被组织成由营养可用性变化激活的集体细胞器模式。化学生物学剖析表明，感知到的生长速率和细胞大小会特异性地激活这些细胞器模式。对细胞质可用性的数学建模和合成控制表明，细胞器模式结构允许在恒定环境中实现生长稳态，并对环境变化做出反应。这种调节结构可能是细胞区室化如何允许细胞大小和生长速率具有灵活性，以满足原本相互矛盾的环境和发育限制的基础。
