Optimality in organelle number and size control under a limiting pool of resources

Among the hallmarks of the eukaryotic cell is its organization into spatially defined subcompartments known as organelles. Organelles provide specialized environments for otherwise incompatible biochemical reactions within the cell. In order to tailor organelle biogenesis to the needs of the cell, the cell can regulate the size and number of many of its organelles. Organelle biogenesis, however, is fundamentally constrained by the limited available pool of resources available to the cell to synthesize its organelles. This begs the question: what principles dictate how much of the cell’s limited resources are devoted to increasing the number versus the size of a given organelle? We find that the solutions to the constrained optimization fall into two regimes separated by a critical point, suggesting that cells face an unexpectedly sharp tradeoff between organelle number and size in resource-limited contexts. In particular we find that the mechanisms governing the biogenesis of a given organelle coincides with whether cells grow the organelle in number versus size. In organelles that are created via de-novo synthesis, the cell appears to grow the total volume of the organelle by increasing the number of organelles with minimal concomitant increase in average organelle size. The situation is reversed in organelles that undergo cycles of fission and fusion. Our theoretical and experimental results are consistent with the idea that cells attempt to allocate organelle number and size to maximize usage of cellular volume available to organelles.