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Neuronal dendrites form densely branched tree architectures through which mitochondria must be distributed to supply the cell's energetic needs. Dendritic mitochondria circulate across the tree, undergoing fusion and fission to form clusters of varying sizes. We present a mathematical model for the distribution of such actively driven interacting particles in a branched geometry, showing that the density and localization of particles is highly sensitive to the fusion/fission balance and to the tree architecture. Our model demonstrates that “balanced” trees (wherein cross-sectional area is conserved across junctions and thicker branches support more bushy subtrees) enable symmetric yet distally enriched particle distributions and promote dispersion into smaller clusters. These results highlight the importance of tree morphology and radius-dependent fusion in governing the distribution of neuronal mitochondria. Published by the American Physical Society2024
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Spatiotemporal Modeling of Mitochondrial Network Architecture
In many cell types, mitochondria undergo extensive fusion and fission to form dynamic, responsive network structures that contribute to a number of homeostatic, metabolic, and signaling functions. The relationship between the dynamic interactions of individual mitochondrial units and the cell-scale network architecture remains an open area of study. In this work, we use coarse-grained simulations and approximate analytic models to establish how the network morphology is governed by local mechanical and kinetic parameters. The transition between fragmented structures and extensive networks is controlled by local fusion-to-fission ratios, network density, and geometric constraints. Similar fusion rate constants are found to account for the very different structures formed by mammalian networks (poised at the percolation transition) and well-connected budding yeast networks. Over a broad parameter range, the simulated network structures can be described by effective mean-field association constants that exhibit a nonlinear dependence on the microscopic nonequilibrium fusion, fission, and transport rates. Intermediate fusion rate constants are shown to result in the highest rates of network remodeling, with mammalian mitochondrial networks situated in a regime of high turnover. This spatially resolved modeling and simulation framework helps elucidate the emergence of cellular scale network structures, and allows for the quantitative extraction of microscopic kinetic parameters from past and future experimental data. Published by the American Physical Society2024
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- PAR ID:
- 10626703
- Publisher / Repository:
- Physical Review X Life
- Date Published:
- Journal Name:
- PRX Life
- Volume:
- 2
- Issue:
- 4
- ISSN:
- 2835-8279
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1103/PRXLife.2.043002
