The coordination of global macromolecular synthesis and organelle biogenesis during cellular growth

Over the course of the growth and maintenance of the eukaryotic cell, the cell is tasked with managing the flow of material to its component parts in a controlled fashion. Among both the chief consumers and sources of these materials in the cell, including proteins and lipids, are its organelles. Despite remarkable progress in our molecular understanding of how the cell can change the rate of global protein and lipid synthesis, it is still unclear how organelles react, both alone and in concert with the other organelles in the cell, upon perturbations to these global material fluxes. Here, we tuned the rates of global protein, lipid, and nucleic acid synthesis in the model organism Saccharomyces cerevisiae and used hyperspectral confocal microscopy to monitor the effects of these perturbations on the systems-level organelle architecture of individual cells. Far from having uniform effects on systems-level organelle biogenesis, reduction in global protein synthesis appears to reveal prioritization of certain organelles over others. At the broadest level, protein synthesis inhibition reduces the fraction of the cell allocated to mitochondria, lipid droplets and Golgi, while increasing vacuoles and peroxisomes, a pattern of reallocation reminiscent of our previous findings documenting systems-level organelle changes in response to altered cell size. Our results thus point to a framework in which we may infer how the cell interprets global material fluxes in coordinating organelle biogenesis with cellular growth.