Fang Yu, Shixing Wang，Ronan Hanley, Peyman Fahimi, Shankar Mukherji
Among the hallmarks of the eukaryotic cell is its organization into spatially defined subcompartments known as organelles. Organelles provide optimized 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? Here, using a combination of theory and experiment, we propose that cellular resource allocation to organelle number and size is consistent with a simple optimality principle: namely that resources are optimally allocated to organelle number and size growth for de novo synthesized organelles, while organelle numbers and sizes themselves are optimized for fission derived organelles. To test this idea, we sought and uncovered signatures in the patterns of organelle number and size that derive from our optimization framework. Our framework predicts that, in contrast to de novo synthesized organelles, fission-mediated organelle biogenesis exhibits critical behavior. Employing hyperspectral imaging to capture systems-level organelle number and size properties for six major organelles simultaneously, we observed distinct signatures of this critical behavior in mitochondria and their absence in Golgi and lipid droplets. This work represents a potential step toward uncovering the general rules that dictate resource allocation decisions during the processes eukaryotic cells use to build their organelles.
* Authors contributed equally.
Shixing Wang, Deepthi Kailash, Shankar Mukherji
A complete framework of eukaryotic cellular growth control must include the growth of its defining hallmarks, spatial compartments known as organelles. Here we map out the correlation structure of systems-level organelle biogenesis with cellular growth using “rainbow yeast”, allowing simultaneous visualization of 6 major metabolically active organelles. Hyperspectral imaging of thousands of single rainbow yeast cells revealed that systems-level organelle biogenesis is organized into collective organelle modes activated by changes in nutrient availability. Chemical biological dissection suggests that the sensed growth rate and size of the cell specifically activate these distinct organelle modes. Mathematical modeling and synthetic biological control of cytoplasmic availability suggests that the organelle mode structure allows the cell to maintain growth homeostasis in constant environments while remaining responsive to environmental change. This regulatory architecture may underlie how compartmentalization allows eukaryotes to flexibly tune cell sizes and growth rates to satisfy otherwise incompatible environmental and developmental constraints.
https://doi.org/10.1093/mnras/stac3291.
https://doi.org/10.1093/mnras/stab718