Dissertation
A nonlinear dynamical systems model for DRP1 oligomerization dependent mitochondrial fission
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Summer 2023
DOI: 10.25820/etd.006892
Abstract
The overall objective of this project is to identify regulatory parameters in the molecular mechanisms impacting mitochondrial dynamics, specifically fission/fusion balance. These regulatory parameters will help therapeutic target selection with the goal of modulating mitochondrial dynamics without inducing extreme hyperfission or hyperfusion. Cellular stress results in fission/fusion imbalance which further leads to reduced energy production and programmed cell death. There is a critical need in mitochondrial biology to understand the molecular mechanisms that coordinate this complex process. Using multi-scale mathematical modeling, we investigate a DRP1 oligomerization dependent fission mechanism in order to identify regulatory parameters for mitochondrial fission.
Based on Dr. Colleen Mitchell’s preliminary mathematical modeling of in vivo and in vitro mitochondrial dynamics which focused on the balance between fission and fusion, the rate of mitochondrial fission is the ideal control point for the distribution of mitochondrial size. We hypothesize
the association and dissociation rate constants for dynamin related protein one (Drp1), a GTPase necessary for fission, and oligomerization on the outer mitochondrial membrane (OMM) are critical for determining the fission rate.
Details
- Title: Subtitle
- A nonlinear dynamical systems model for DRP1 oligomerization dependent mitochondrial fission
- Creators
- Anna Kay Leinheiser
- Contributors
- Colleen C Mitchell (Advisor)Chad Eric Grueter (Committee Member)Stefan Strack (Committee Member)Bruce Ayati (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Applied Mathematical and Computational Sciences
- Date degree season
- Summer 2023
- DOI
- 10.25820/etd.006892
- Publisher
- University of Iowa
- Number of pages
- xvi, 179 pages
- Copyright
- Copyright 2023 Anna Kay Leinheiser
- Language
- English
- Date submitted
- 07/25/2023
- Description illustrations
- illustrations (some color)
- Description bibliographic
- Includes bibliographical references (pages 170-179).
- Public Abstract (ETD)
This project works to identify regulatory parameters in the molecular mechanisms impacting mitochondrial activity, specifically fission/fusion balance. Cellular stress causes fission/fusion imbalance which leads to reduced energy production and programmed cell death, hence the critical need to identify parameters that maintain this balance. Using multi-scale mathematical modeling, we investigate a Drp1 oligomerization dependent fission mechanism in order to identify regulatory parameters for mitochondrial fission. The mathematical model serves as a building block for future experimentalists.
- Academic Unit
- Interdisciplinary Graduate Program in Applied Mathematical & Computational Sciences
- Record Identifier
- 9984454186102771
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