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- All Subjects: Mitochondria
- Creators: Angell, Charles A
Description
This thesis critically examines the scientific and ethical dimensions of the novel and controversial technology of mitochondrial replacement therapy (MRT). The first portion provides a background on mitochondrial diseases and examines how these organelles (mitochondria) have left humans vulnerable to disease. The second portion of the thesis examines the technology of mitochondrial replacement therapy and what research contributed to the development of MRT. Finally, the third section responds to the ethical and legal concerns proposed and outlined by the Nuffield Council of Bioethics. After careful consideration of all legal and ethical concerns, it is concluded that the technology of MRT should be pursued under careful foresight with the idea that the technology is already happening and we must move forward in a way that provides the greatest information.
ContributorsLee, Giselle Alexandra (Author) / Fette, Donald (Thesis director) / Hurlbut, Ben (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Mitochondria produce the majority portion of ATP required in eukaryotic cells. ATP is generated through a process known as oxidative phosphorylation, through an pathway consisting five multi subunit proteins (complex I-IV and ATP synthase), embedded inside the mitochondrial membrane. Mitochondrial electron transport chain dysfunction increases reactive oxygen species in the cell and causes several serious disorders. Described herein are the synthesis of antioxidant molecules to reduce the effects in an already dysfunctional system. Also described is the study of the mitochondrial electron transport chain to understand the mechanism of action of a library of antioxidants. Illustrated in chapter 1 is the general history of research on mitochondrial dysfunction and reported ways to ameliorate them. Chapter 2 describes the design and synthesis of a series of compounds closely resembling the redox-active quinone core of the natural product geldanamycin. Geldanamycin has been reported to confer cytoprotection to FRDA lymphocytes in a dose dependent manner under conditions of induced oxidative stress. A library of rationally designed derivatives has been synthesized as a part of our pursuit of a better neuroprotective drug. Chapter 3 describes the design and synthesis of a library of pyrimidinol analogues. Compounds of this type have demonstrated the ability to quench reactive oxygen species and sustain mitochondrial membrane potential. Described herein are our efforts to increase their metabolic stability and total ATP production. It is crucial to understand the nature of interaction between a potential drug molecule and the mitochondrial electron transport chain to enable the design and synthesis a better therapeutic candidates. Chapter 4 describes a part of the enzymatic
binding studies between a molecular library synthesized in our laboratory and the mitochondrial electron transport chain using sub mitochondrial particles (SMP).
binding studies between a molecular library synthesized in our laboratory and the mitochondrial electron transport chain using sub mitochondrial particles (SMP).
ContributorsDey, Sriloy (Author) / Hecht, Sidney M. (Thesis advisor) / Angell, Charles A (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2015