Journal article
A dynamical systems model for the total fission rate in Drp1-dependent mitochondrial fission
PLoS computational biology, Vol.20(11), e1012596
11/18/2024
DOI: 10.1371/journal.pcbi.1012596
PMCID: PMC11611272
PMID: 39556606
Abstract
Mitochondrial hyperfission in response to cellular insult is associated with reduced energy production and programmed cell death. Thus, there is a critical need to understand the molecular mechanisms coordinating and regulating the complex process of mitochondrial fission. We develop a nonlinear dynamical systems model of dynamin related protein one (Drp1)-dependent mitochondrial fission and use it to identify parameters which can regulate the total fission rate (TFR) as a function of time. The TFR defined from a nondimensionalization of the model undergoes a Hopf bifurcation with bifurcation parameter μ = k + M k - where M is the total concentration of mitochondrial fission factor (Mff) and k + and k − are the association and dissociation rate constants between oligomers on the outer mitochondrial membrane. The variable μ can be thought of as the maximum build rate over the disassembling rate of oligomers. Though the nondimensionalization of the system results in four dimensionless parameters, we found the TFR and the cumulative total fission (TF) depend strongly on only one, μ . Interestingly, the cumulative TF does not monotonically increase as μ increases. Instead it increases with μ to a certain point and then begins to decrease as μ continues to increase. This non-monotone dependence on μ suggests interventions targeting k + , k − , or M may have a non-intuitive impact on the fission mechanism. Thus understanding the impact of regulatory parameters, such as μ , may assist future therapeutic target selection.
Details
- Title: Subtitle
- A dynamical systems model for the total fission rate in Drp1-dependent mitochondrial fission
- Creators
- Anna K. Leinheiser - University of Iowa, Internal MedicineColleen C. Mitchell - University of IowaEthan Rooke - University of Iowa, Psychological and Brain SciencesStefan Strack - University of IowaChad E. Grueter - University of Iowa
- Contributors
- Daniel A Beard (Editor)
- Resource Type
- Journal article
- Publication Details
- PLoS computational biology, Vol.20(11), e1012596
- DOI
- 10.1371/journal.pcbi.1012596
- PMID
- 39556606
- PMCID
- PMC11611272
- NLM abbreviation
- PLoS Comput Biol
- ISSN
- 1553-7358
- eISSN
- 1553-7358
- Publisher
- PUBLIC LIBRARY SCIENCE; SAN FRANCISCO
- Grant note
- American Heart Association Transformational Project Award: 969976
This work was partially supported by the American Heart Association Transformational Project Award (969976 to CEG) (https://www.heart. org). The funders had no role in the design, collection, analysis, publication, or preparation of the manuscript.
- Language
- English
- Date published
- 11/18/2024
- Academic Unit
- Psychological and Brain Sciences; Pathology; Iowa Neuroscience Institute; Cardiovascular Medicine; Craniofacial Anomalies Research Center; Fraternal Order of Eagles Diabetes Research Center; Computer Science; Mathematics; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984749496302771
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