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Open Access Publications from the University of California

Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UC Irvine Electronic Theses and Dissertations (2023)

The transfer of mitochondria, whether through natural or artificial pathways, has been experimentally validated across various cell lines, demonstrating potential benefits for host cells experiencing mitochondrial dysfunction. However, conflicting reports suggest that our understanding of the outcomes of mitochondria transfer in host cells remains incomplete. This dissertation aims to delve into the concept of mitochondria transfer and examine its effects on metabolism, viability, and oxidative stress in breast cancer host cells. The novelty of this dissertation lies in the utilization of fluorescence lifetime imaging to analyze the metabolic profiles of individual mitochondria. Through the combination of fluorescence labeling and NADH lifetime imaging, we have discovered that newly formed mitochondria in breast cancer host cells exhibit an increase in the bound fraction of NADH, indicating a reliance on Oxidative Phosphorylation (OXPHOS). While the enhancement of OXPHOS leads to heightened respiration and proliferation, the accumulation of reactive oxygen species (ROS) levels surpasses the tolerance threshold of breast cancer cells towards oxidative stress, resulting in elevated drug sensitivity when exposed to anticancer drugs. The significance of this dissertation resides in its multifaceted approach, shedding light on the impact of mitochondria transfer and establishing new methodologies for future research endeavors.

    Cover page: Evaluating Mitochondria Transfer, Energy Metabolism, ROS Accumulation, and Development of Fluctuation Correlation using the side-SPIM
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2022)
    Oxidative stress mediated by reactive oxygen species (ROS) is a key process for adverse aerosol health effects. Secondary organic aerosols (SOA) account for a major fraction of fine particulate matter, and their inhalation and deposition into the respiratory tract causes the formation of ROS by chemical and cellular processes, but their relative contributions are hardly quantified and their link to oxidative stress remains uncertain. Here, we quantified cellular and chemical superoxide generation by 9,10-phenanthrenequinone (PQN) and isoprene SOA using a chemiluminescence assay combined with electron paramagnetic resonance spectroscopy as well as kinetic modeling. We also applied cellular imaging techniques to study the cellular mechanism of superoxide release and oxidative damage on cell membranes. We show that PQN and isoprene SOA activate NADPH oxidase in macrophages to release massive amounts of superoxide, overwhelming the superoxide formation by aqueous chemical reactions in the epithelial lining fluid. The activation dose for PQN is 2 orders of magnitude lower than that of isoprene SOA, suggesting that quinones are more toxic. While higher exposures trigger cellular antioxidant response elements, the released ROS induce oxidative damage to the cell membrane through lipid peroxidation. Such mechanistic and quantitative understandings provide a basis for further elucidation of adverse health effects and oxidative stress by fine particulate matter.
      Cover page: Superoxide Release by Macrophages through NADPH Oxidase Activation Dominating Chemistry by Isoprene Secondary Organic Aerosols and Quinones to Cause Oxidative Damage on Membranes.
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