Mathematical Modeling and Computational Simulation of Metabolic Regulation of Mitochondrial Dynamics in Aging

• Main Authors: Chen Chang, 張辰
• Other Authors: An-Chi Wei
• Format: Others
• Language: en_US
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/dppk2q

碩士 === 國立臺灣大學 === 生醫電子與資訊學研究所 === 107 === Recent studies have demonstrated the importance of metabolic regulations on mitochondrial dynamics. Still, existing literature lacks a methodology to assimilate different experimental data and fully understand the interplay between bioenergetics and organelle behavior. This thesis adopts an in silico method that integrates the current knowledge about the molecular mechanism of mitochondrial dynamics, including fusion, fission, transport, biogenesis, and mitophagy. Notably, a multi-method mathematical model that was implemented, simulating the bioenergetic shift in the aging process to study how the metabolic shift regulates the mitochondrial dynamics. The model contains two parts: mitochondrial metabolism and mitochondrial dynamics. The ordinary differential equation based metabolic model simulates the bioenergetics of mitochondria with an output of GTP level and ADP/ATP ratio, which regulate the mitochondrial fission-fusion cycle. Subsequently, the simulated fission-fusion parameters are applied in the stochastic agent-based mitochondrial dynamics model. Overall, this project pursues a model that not only predicts the dynamics of mitochondria under varying physiological conditions for further experimentation, but also understand the interplay between metabolism and mitochondrial dynamics. The proposed model is expected to further our understanding of alterations in mitochondrial dynamics in disease progression and aging.