Consequences of Persistent Mitochondrial DNA Damage and Increased Oxidative Stress
Public Deposited- Last Modified
- February 26, 2019
- Creator
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Donoghue, Lauren
- Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
- Abstract
- Environmental toxicants such as polycyclic aromatic hydrocarbons can cause irreparable mitochondrial DNA damage. Mitochondria play a critical role in energy production and aging. Mitochondrial dysfunction has been associated with diseases occurring in 1 in 4,000 individuals. In C. elegans nematodes, persistent mitochondrial DNA damage during development from exposure to ultraviolet C (UVC) irradiation results in delays in development, reduced ATP production and reduced oxygen consumption and, thus, suggesting dysfunction of the electron transport chain (ETC). The mechanism by which UVC irradiation causes these effects is unclear; one hypothesis is that UVC irradiation-induced mitochondrial dysfunction results in production of reactive oxygen species (ROS). Both ETC dysfunction and UVC exposure can increase levels of ROS associated with increased cellular damage and homeostatic cell signaling. I investigated the larval arrest, growth, genome copy number, and regulation of unfolded protein responses by heat shock proteins in superoxide dismutase (SOD) mutant C. elegans with persistent mitochondrial DNA damage to investigate the potential role of increased oxidative stress. Development delay, growth inhibition, and a decrease in mitochondrial-to-nuclear genome copy number, were seen in UVC-exposed mitochondrial SOD mutants compared to UVC-exposed wild-type while cytosolic SOD mutants exhibited altered phenotypes similar to wild-type. No nematode strains showed significant upregulation of mitochondrial, endoplasmic reticulum, or cytosolic heath shock proteins. These results suggest that UVC exposure specifically affects mitochondria and that the effects of the mitochondrial DNA damage are exacerbated by decreased defense against damage caused by mitochondrial superoxide. Further experiments are needed to determine the mechanism(s) that contribute to these altered phenotypes and the extent of ETC dysfunction due to persistent mitochondrial DNA damage caused by UVC irradiation.
- Date of publication
- spring 2014
- Keyword
- DOI
- Resource type
- Rights statement
- In Copyright
- Note
- Funding: NIH, Duke University Superfund Research Center
- Advisor
- Nylander-French, Leena A.
- Degree
- Bachelor of Science in Public Health
- Honors level
- Highest Honors
- Degree granting institution
- University of North Carolina at Chapel Hill
- Extent
- 57
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