Temporal Regulation of Organelle Biogenesis

AbstractOrganelle abundance is tightly regulated in eukaryotic cells in response to external stimuli. The underlying mechanisms responsible for this regulation remains less understood. Time-lapse imaging of fluorescently labelled organelles allow for counting individual organelle copies at a single-cell level. These experiments contain information about the time evolution of distribution of organelle number across a population of cells. To tap onto such data, we build upon a recently proposed kinetic model of organelle biogenesis that explicitly incorporates de novo synthesis, fission, fusion and degradation of organelles. Different limits of this general model correspond to distinct mechanisms of organelle biogenesis. We compute the first two moments of organelle number distribution for these different mechanisms. Interestingly, different mechanisms of biogenesis lead to qualitatively distinct temporal behavior of cell-to-cell variability (noise), thereby allowing us to discern between these mechanisms. Notably, noise in temporal organelle abundance exhibits strikingly more complex behaviour as compared to the steady state. Our modeling framework paves the way for extracting quantitative information about the dynamics of organelle biogenesis from time-lapse experiments that can measure organelle abundance at single-molecule resolution.