Speaker
Description
Mitochondrial networks range from fragmented to hyperfused, spatially organised to meet energetic and signalling demands \cite{Chen2023}. Cycles of fission, fusion, biogenesis, mitophagy, and motility (termed mitochondrial dynamics) underpin the capacity for homeostasis and quality control, yet mechanistic frameworks interrogating these emergent properties are scarce \cite{Kowald2014,Dalmasso2017,Holt2024,Fogo2025}. We present a hybrid spatial agent-based model of mitochondrial dynamics where nodes evolve via overdamped Langevin dynamics with active transport and dynamic graphs capture remodelling. The model couples motion, collision, and local fission-fusion rules to probe how mechanics and motility shape networks. Population-level distributions, fission-fusion rates, graph metrics, and trajectory statistics facilitate comparison with segmented widefield time-lapse data. Validation in mammalian cultures yields three insights: (i) cumulative remodelling is driven by accumulation of discrete fission events exceeding fusion, (ii) correlated fission-fusion rates suggest rapid reciprocal priming of events, and (iii) spatial spread depends on cellular context and transport dynamics. This quantitative framework enables hypothesis testing and parameter inference to explore how mitochondrial dynamics influence cell-level behaviours such as cell polarity, energy supply, and migration.
Bibliography
@article{Chen2023,
author = {Chen, Wen and Zhao, Huakan and Li, Yongsheng},
title = {Mitochondrial dynamics in health and disease: mechanisms and potential targets},
journal = {Signal Transduction and Targeted Therapy},
year = {2023},
volume = {8},
pages = {333},
doi = {10.1038/s41392-023-01547-9},
url = {https://www.nature.com/articles/s41392-023-01547-9}
}
@inbook{Kowald2014,
author = {Kowald, Axel and Klipp, Edda},
title = {Mathematical models of mitochondrial aging and dynamics},
booktitle = {Progress in Molecular Biology and Translational Science},
publisher = {Elsevier},
year = {2014},
volume = {127},
pages = {63--92},
doi = {10.1016/B978-0-12-394625-6.00003-9},
url = {https://linkinghub.elsevier.com/retrieve/pii/B9780123946256000039}
}
@article{Dalmasso2017,
author = {Dalmasso, Giovanni and Marin Zapata, Paula Andrea and Brady, Nathan Ryan and Hamacher-Brady, Anne},
title = {Agent-based modeling of mitochondria links sub-cellular dynamics to cellular homeostasis and heterogeneity},
journal = {PLOS ONE},
year = {2017},
volume = {12},
pages = {e0168198},
doi = {10.1371/journal.pone.0168198},
url = {https://dx.plos.org/10.1371/journal.pone.0168198}
}
@article{Holt2024,
author = {Holt, Keaton B. and Winter, Julius and Manley, Suliana and Koslover, Elena F.},
title = {Spatiotemporal modeling of mitochondrial network architecture},
journal = {PRX Life},
year = {2024},
volume = {2},
pages = {043002},
doi = {10.1103/PRXLife.2.043002},
url = {https://link.aps.org/doi/10.1103/PRXLife.2.043002}
}
@article{Fogo2025,
author = {Fogo, Garrett M. and Torres Torres, Francisco J. and Speas, Reagan L. and Anzell, Anthony R. and Sanderson, Thomas H.},
title = {Agent-based modeling of neuronal mitochondrial dynamics using intrinsic variables of individual mitochondria},
journal = {iScience},
year = {2025},
volume = {28},
pages = {112390},
doi = {10.1016/j.isci.2025.112390},
url = {https://linkinghub.elsevier.com/retrieve/pii/S2589004225006510}
}
