UC Irvine

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.