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Biophysics and Soft Matter Seminar
Topology and transport in dynamic mitochondrial networks
Keaton Holt, Dept. of Physics, University of California, San Diego
Location: SSB 7172
Synopsis
In many eukaryotic cells, mitochondria undergo fusion, fission, and motor-based transport to form extensive, 3-dimensional spatial networks which rearrange on the timescale of a few minutes. These networks exhibit myriad structural and dynamical states depending on nutrient condition, genetic perturbation, disease state, and cell cycle stage. The precise link between structure and function, however, remains unclear. We employ physical models to explore emergent network architecture in a variety of cellular geometries and its role in the dynamic homogenization of mitochondrial contents.
In the budding yeast S.cerevisiae, mitochondrial networks are confined to the 2D inner surface of the cell membrane, becoming longer, more branched, and more highly looped as the cell grows. We construct a simple mathematical model that can quantitatively account for these patterns by formulating network structure as a balance of fusion and fission over timescales much faster than the network growth.
While the balance of fusion and fission defines the physical layout of the network across the cell cycle, it also establishes the structural and dynamical framework that dictates how biomolecules are distributed throughout the mitochondrial population. We show theoretically that the dispersion of diffusive material through a dynamic network is governed by a balance of competing timescales: the encounter rate of distinct mitochondria in space and the rate of filling of individual mitochondria by biomolecular diffusion through a fractal continuum. We test these predictions by quantitatively comparing the spread of photoconverted proteins in live cell imaging with our analytic predictions and spatially resolved simulations.