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Uncovering the principles coordinating systems-level organelle biogenesis with cellular growth

Among the hallmark properties of the eukaryotic cell is its organization into specialized biochemical compartments known as organelles. Understanding how organelle biogenesis at systems-scale is coordinated with cellular growth rate and size is a major goal of quantitative cell biology. Here we map out the correlation structure of systems-level organelle biogenesis with cellular growth using “rainbow yeast”, a strain of Saccharomyces cerevisiae that expresses fluorescent labels for 6 major organelles. By carrying out hyperspectral imaging of thousands of single rainbow yeast cells, we decomposed the systems-level organelle biogenesis program into specific modes that characterize the response to changes in nutrient availability. Upon chemical biological dissection of this response, our results suggest that systems-level organelle biogenesis represents the sum of distinct organelle modes excited by growth rate and cell size separately. The flexibility afforded by this regulatory architecture may underlie how eukaryotic cells leverage compartmentalization to independently tune cell sizes and growth rates and satisfy potentially incompatible environmental and developmental constraints.