Building and maintaining a System of Intracellular Compartments

arXiv:2604.12930v2 Announce Type: replace-cross
Abstract: Organelle patterning and its heritability remain central mysteries in cell biology, highlighting the fundamental tension between genetic inheritance and self-assembly. Here, we explore the nonequilibrium assembly and emdedded size control of the Golgi cisternae and endosomes, amid a continuous flux of membrane traffic, within a stochastic framework of mechanochemical fusion-fission cycles that violate detailed balance. Using a dynamical systems approach, we identify distinct, robust regimes, ranging from fixed points to limit cycles with definite phase relations between cisternae. We identify these dynamical regimes with diverse phenotypes, from stable cisternae to periodic, cell-cycle-dependent dissolution/reassembly of cisternae to cisternal progression. We analyse its dynamic response to systematic perturbations or driving protocols and make definite predictions that may be tested experimentally. Our analysis reveals that the two competing models of Golgi organization – vesicular transport and cisternal progression – are, in fact, two phases of the same underlying nonequilibrium process. We see that cisternal size homeostasis is brought about by a size-dependent embedded control system driven by fusion-fission kernels. Finally, our framework offers a strategy for controlling cisternal number and chemical identity by modulating the interplay between glycosylation enzymes and membrane fission-fusion dynamics.