• About
    • Login
    View Item 
    •   Institutional Repository Home
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations
    • View Item
    •   Institutional Repository Home
    • Electronic Theses and Dissertations
    • Electronic Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Institutional RepositoryCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Investigating mitochondrial deoxyribonucleotide metabolism and its role in a family of genetic diseases

    Gandhi, Vishal V
    : https://etd.library.vanderbilt.edu/etd-11292011-142606
    http://hdl.handle.net/1803/14867
    : 2011-12-01

    Abstract

    Abnormal regulation of mitochondrial deoxyribonucleoside triphosphate pools can lead to mitochondrial DNA depletion syndromes, a set of genetic diseases associated with depletion of mitochondrial DNA. Besides mitochondrial DNA depletion syndromes, improper maintenance of mitochondrial deoxyribonucleoside triphosphate pools and mitochondrial DNA have also been implicated in a host of other human pathologies. The unifying objective of this dissertation was to enhance our knowledge of the regulation of mitochondrial deoxyribonucleoside triphosphate pools. The first step was to investigate the characteristics of mitochondrial and cytoplasmic deoxyribonucleoside triphosphate levels. I calculated mitochondrial and cytoplasmic deoxyribonucleoside triphosphate concentrations from previously published data. Cytoplasmic and mitochondrial deoxyribonucleoside triphosphates are strongly correlated in normal cells but not in transformed cells. Following up this discovery with analysis of gene expression, I discovered that, consistent with the trends in deoxyribonucleoside triphosphate concentrations in cells, genes coding for enzymes that maintain cytoplasmic and mitochondrial deoxyribonucleoside triphosphates have correlated expression across normal tissues but not across transformed tissues. To further understand the influence of cytoplasmic deoxyribonucleoside triphosphates on mitochondrial deoxyribonucleoside triphosphates, I simulated the metabolism of mitochondrial deoxyribonucleosides with a computational model. Cytoplasmic deoxyribonucleotides have a substantial and indispensable contribution to mitochondrial deoxyribonucleoside triphosphates in most circumstances. My results further show that import from the cytoplasm would need to occur at either deoxyribonucleoside diphosphate or triphosphate levels.
    Show full item record

    Files in this item

    Icon
    Name:
    Gandhi.pdf
    Size:
    2.700Mb
    Format:
    PDF
    View/Open

    This item appears in the following collection(s):

    • Electronic Theses and Dissertations

    Connect with Vanderbilt Libraries

    Your Vanderbilt

    • Alumni
    • Current Students
    • Faculty & Staff
    • International Students
    • Media
    • Parents & Family
    • Prospective Students
    • Researchers
    • Sports Fans
    • Visitors & Neighbors

    Support the Jean and Alexander Heard Libraries

    Support the Library...Give Now

    Gifts to the Libraries support the learning and research needs of the entire Vanderbilt community. Learn more about giving to the Libraries.

    Become a Friend of the Libraries

    Quick Links

    • Hours
    • About
    • Employment
    • Staff Directory
    • Accessibility Services
    • Contact
    • Vanderbilt Home
    • Privacy Policy