Systems-level interdependence in organelle biogenesis

Eukaryotic cells contain hundreds of subcellular structures that serve different functions to maintain cellular homeostasis. A hallmark of Eukaryotic cells is its compartmentalization into membrane-bound organelles. While the function of individual organelles and their role in cellular homeostasis is well studied, less is known about the cell's coordinated control over their synthesis. Recent discoveries have unveiled the mechanisms by which cells regulate the size and abundance of individual membranous organelles. However, we know little about the autonomy or dependence of growth amongst different types of organelles. Here we have characterized the systems-level patterns of interdependence in organelle biogenesis using Saccharomyces cerevisiae as a model system. We have engineered budding yeast cells to fluorescently label six of their membranous organelles simultaneously and imaged them using confocal hyperspectral microscopy. By perturbing genetic factors involved in the biogenesis of each individual organelle, we measured the response in the growth of other organelles. Our statistical analyses revealed a correlation between the growth of mitochondria and the endoplasmic reticulum (ER), the ER and peroxisomes, and mitochondria and peroxisomes. We will incorporate these correlations into our mathematical model of organelle biogenesis control as a step toward capturing the principles by which the cell allocates its finite resources during growth and homeostasis.