Mechanisms of organelle biogenesis govern stochastic fluctuations in organelle copy number

Among the defining properties of the eukaryotic cell is its organization into spatial compartments known as organelles, specialized biochemical environments crucial for processes fundamental to life. Coordinating organelle copy number, size, and composition with developmental and environmental cues is one of the chief ways the cell can match its biochemical capabilities with its physiological demands. How precisely does the cell orchestrate flows of matter and energy to produce exquisitely defined organelles at the nanometer and femtoliter scales of a cell? Using a stochastic model of organelle copy number control, we show that cell-to-cell fluctuations in budding yeast organelle copy numbers can be used to infer the mechanisms by which organelle copy numbers are regulated. We show how our fluctuation-based inferences suggest resolutions to controversies surrounding the biogenesis of peroxisomes and lipid droplets, organelles responsible for major steps in lipid metabolism. By studying correlations in fluctuations of distinct organelles, we hope to infer the decision-making principles cells utilize to remodel their organelle makeup to respond to external signals.