Ferroptosis-Like Death Induction in <i>Saccharomyces cerevisiae</i> by Gold Nanoparticles

Ferroptosis, a novel form of regulated cell death (RCD), has emerged as a promising therapeutic strategy for cancer treatment. While gold nanoparticles (AuNPs) are known to induce cell death and ferroptosis in combination with certain antibiotics, the mechanisms underlying ferroptosis in microorganisms remain poorly understood. This study aimed to investigate whether AuNPs induce ferroptosis-like cell death in the eukaryotic microbe <i>Saccharomyces cerevisiae</i>. Our findings revealed that AuNPs significantly reduced cell viability in <i>S. cerevisiae</i>, suggesting their ability to trigger cell death. Ferroptosis-related precursors, including intracellular iron overload and depletion of glutathione (GSH), were observed, leading to the inactivation of glutathione peroxidase (GPx). These changes were associated with the accumulation of reactive oxygen species (ROS) and lipid peroxidation, which amplified oxidative stress within the cells. Elevated ROS levels and lipid peroxidation further resulted in membrane rupture and the formation of 8-hydroxydeoxyguanosine, indicating DNA damage. Mitochondrial dysfunction, a hallmark of ferroptosis, was also evident. AuNP treatment caused mitochondrial membrane potential hyperpolarization and a reduction in mitochondrial membrane density. Unlike previously characterized forms of RCD, ferroptosis-like death in <i>S. cerevisiae</i> did not involve chromatin condensation, DNA fragmentation, or metacaspase activation. Finally, ferroptosis-like characteristics were confirmed using Liperfluo, a lipid ROS-specific probe. In conclusion, this study demonstrated that AuNPs can induce ferroptosis-like cell death in <i>S. cerevisiae</i>. These findings highlight the potential of AuNPs as antifungal agents and contribute to the broader understanding of ferroptosis in eukaryotic microbes.