Robustness and universality in organelle size control

Abstract

Among the most important processes in the self-assembly of the eukaryotic cell is the synthesis of its organelles, specialized biochemical compartments that house processes crucial to cellular physiology. A critical property that governs organelle function is its size. Numerous molecular factors that regulate the sizes of a diverse array of organelles, including the Golgi, mitochondria, peroxisomes and lipid droplets among others, have been identified. However, our understanding of the quantitative principles governing organelle size control remains incomplete. Here, we combine organelle size data from the single-celled eukaryote Saccharomyces cerevisiae and mathematical theory to show that cells can robustly control organelle size fluctuations across a range of organelle sizes. In particular, our framework suggests that organelle size increases in random bursts from a limited pool of building blocks. Bursty organelle growth allows the cell to decouple the average magnitude of organelle size fluctuations from mean organelle size, provided the bursts do not deplete the pool of building blocks from which organelles grow. Bursty growth thus provides a potentially general mechanism by which cells can regulate the noise of the sizes of its subcellular structures.

Analysis of biological noise in the flagellar length control system

“…Considering, as above, the number of protofilaments in the flagellum, the effective monomer size for a fluctuation of 0.7 mm would correspond to approximately 20,000 tubulin dimers. Such large steps cannot correspond to individual tubulin dimer assembly or dissociation events, but rather to ''bursts'' of assembly or disassembly, as have been described in studies of transcriptional noise (Sanchez and Golding, 2013) and invoked in models of organelle biogenesis (Amiri et al, 2020). One possibility is that the random walk is driven by microtubule dynamic instability, in which periods of processive growth alternate with periods of processive shrinkage.…”

“…Cell-to-cell variation in organelle size and number has been observed in genetically identical cells (Marshall, 2007;Mukherji and O'Shea, 2014;Marshall, 2017, 2019). For example, analysis of variation in the copy number of various organelles, as well as joint variation in organelle number and size, has been used to gain insight into the mechanisms of organelle fission, fusion, and inheritance (Mukherji and O'Shea, 2014;Amiri et al, 2020).…”

Overcoming the Challenges to Enhancing Experimental Plant Biology With Computational Modeling

“…Pattern models can reveal these interactions, while mechanistic mathematical models can test them. One of the strongest benefits of mechanistic mathematical modeling is the ability to incorporate multi-disciplinary concepts, such as chemistry (Hills et al, 2012 ; Dale and Kato, 2016 ), biophysics (Deinum et al, 2012 ; Amiri et al, 2019 ; Dreyer et al, 2019 ), and multi-scale processes (Feller et al, 2015 ). Biological systems are necessarily controlled by chemical and physical processes, and in certain cases these effects should not be ignored.…”

Level crossing statistics in a biologically motivated model of a long dynamic protrusion: passage times, random and extreme excursions

“…Our study is motivated by long cell protrusions like eukaryotic flagellum and cilium, which are essentially one-dimensional dynamic structures [23][24][25][26][27][28][29][30][31][32][33]. For proper biological function, size matters at all levels of biological organization [34][35][36][37][38][39][40] and in the case of long cell protrusions, length is the dominant characteristic of their size.…”