Shixing Wang, Deepthi Kailash, Shankar Mukherji
A complete framework of eukaryotic cellular growth control must include the growth of its defining hallmarks, spatial compartments known as organelles. Here we map out the correlation structure of systems-level organelle biogenesis with cellular growth using “rainbow yeast”, allowing simultaneous visualization of 6 major metabolically active organelles. Hyperspectral imaging of thousands of single 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 the sensed growth rate and size of the cell specifically activate these distinct organelle modes. Mathematical modeling and synthetic biological control of cytoplasmic availability suggests that the organelle mode structure allows the cell to maintain growth homeostasis in constant environments while remaining responsive to environmental change. This regulatory architecture may underlie how compartmentalization allows eukaryotes to flexibly tune cell sizes and growth rates to satisfy otherwise incompatible environmental and developmental constraints.