Date of Award

August 2020

Degree Type

Thesis

Degree Name

Master of Science

Department

Engineering

First Advisor

Devendra Misra

Second Advisor

Ranjan Dash

Committee Members

Veysi Malkoc

Keywords

Computational Biology, Mitochondria, OMM, Outer mitochondrial membrane, VDAC, Voltage Dependent Anion Channel

Abstract

The voltage-dependent anion channel (VDAC) is a voltage gated channel residing on the outer mitochondrial membrane (OMM) that facilitates the flow of metabolites between the cytosol and mitochondria. The channel is regulated through conformational changes driven by electrostatic effects along with numerous regulatory mechanisms. The aim of this study is to mechanistically model kinetics of substrate flow through VDAC and incorporate them into existing mechanistic computational models of mitochondrial function. The resulting model is used in two ways: 1) to establish mitochondrial bioenergetics (conductance, permeability, and current/flux) under physiological conditions, and 2) to conduct perturbations simulating the effect of altered VDAC kinetics (resulting in altered membrane permeabilities and substrate fluxes) by cellular regulatory changes (such channel closure) on overall mitochondrial function.

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