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Mitochondrial Involvement In Neuronal Cell Death, Josie J. Gray Aug 2014

Mitochondrial Involvement In Neuronal Cell Death, Josie J. Gray

Electronic Theses and Dissertations

Neuronal cell death via apoptosis or necrosis underlies several devastating neurodegenerative diseases associated with aging. Mitochondrial dysfunction resulting from oxidative or nitrosative stress often acts as an initiating stimulus for intrinsic apoptosis or necrosis. These events frequently occur in conjunction with imbalances in the mitochondrial fission and fusion equilibrium, although the cause and effect relationships remain elusive. In this thesis, I demonstrate in primary rat cerebellar granule neurons (CGNs) that oxidative or nitrosative stress induces an N-terminal cleavage of optic atrophy-1 (OPA1), a dynamin-like GTPase that regulates mitochondrial fusion and maintenance of cristae architecture. This cleavage event is indistinguishable from …


Mitochondrial Replication From Embryogenesis To Early Adulthood, In Dui Species, Mytilus Galloprovincialis, Ellen Blenn Richardson Jan 2014

Mitochondrial Replication From Embryogenesis To Early Adulthood, In Dui Species, Mytilus Galloprovincialis, Ellen Blenn Richardson

Theses and Dissertations

Eukaryotes typically inherit mitochondria strictly maternally. There are however a group of bivalve molluscs that inherit different mitochondrial genomes from each parent. The paternally inherited mtDNA (M-type) is localized to, and dominates over the maternally inherited mtDNA (F-type) in the gonads of the male offspring, but is not normally retained in any tissue of the female offspring. This process is termed Double Uniparental Inheritance (DUI). Using quantitative PCR (qPCR), this study examines mtDNA replication compared to total DNA replication through embryonic stages of development and into early adulthood of the DUI species, Mytilus galloprovincialis. Results indicate that up through the …


Mitochondrial Structure And Function As A Therapeutic Target In Malignant Mesothelioma, Brian Cunniff Jan 2014

Mitochondrial Structure And Function As A Therapeutic Target In Malignant Mesothelioma, Brian Cunniff

Graduate College Dissertations and Theses

Malignant mesothelioma (MM) is a rare tumor associated with occupational exposure to asbestos with no effective treatment regime. Evaluation of mitochondrial function in human MM cell lines revealed a common tumor phenotype: in comparison to immortalized or primary human mesothelial cells, MM tumor cells displayed a more oxidized mitochondrial environment, increased expression of mitochondrial antioxidant enzymes, and altered mitochondrial metabolism. Earlier work by our laboratory indicated that increases in mitochondrial reactive oxygen species (mROS) in MM cell lines supports expression of FOXM1, an oncogenic transcription factor that contributes to increased cell proliferation and chemoresistance. These studies sought to investigate targeting …