Theses and Dissertations

Date of Award

7-2017

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Dr. Robert Gilkerson

Second Advisor

Dr. Megan Keniry

Third Advisor

Dr. Michael Persans

Abstract

Mitochondria form an organellar network to provide ATP to the cell. Mitochondrial DNA (mtDNA) combines with nuclear DNA to encode polypeptides critical to forming the complexes of oxidative phosphorylation in the mitochondrial inner membrane, which generate a transmembrane potential (ΔΨm) to synthesize ATP. This ΔΨm is required to maintain mitochondria fission/fusion dynamics: organellar fusion (mediated by OPA1) and fission events (mediated by DRP1) coordinately regulate mitochondrial dynamics. While oxidative stress correlates with mitochondrial dysfunction, it is unclear how oxidants affect mitochondrial structure/function homeostasis. This project seeks to establish and examine the impact of reactive oxygen species (ROS) on mitochondrial dynamics. Data using 143B human osteosarcoma and H9c2 cardiomyoblast cell lines show fragmentation of the mitochondrial network in both when treated with hydrogen peroxide (H2O2), an ROS donor. Strikingly, however, mechanistic differences were observed. H9c2 cells showed a loss of ΔΨ m and L-OPA1 cleavage however, 143B cells did not show significant L-OPA1 cleavage but did show a redistribution of DRP1. Taken together, these findings indicate that oxidative insults disrupt mitochondrial dynamics, with more profound effects on highly oxidative cell lines as is the case with H9c2 cells.

Comments

Copyright 2017 Iraselia A. Garcia. All Rights Reserved.

https://www.proquest.com/dissertations-theses/oxidative-insults-disrupt-mitochondrial-dynamics/docview/1964970211/se-2?accountid=7119

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