ROS-independent toxicity of Fe3O4 nanoparticles to yeast cells: Involvement of mitochondrial dysfunction.

Fe3O4 nanoparticles, one kind of magnetic nanomaterials (NMs), are widely used in drug delivery, biological imaging, sensors, catalysts and pollution management. However, its toxicity to biological systems and related toxicity mechanisms remain to be explored. In this study, we investigate the effect of as-synthesized Fe3O4 nanoparticles on growth of Saccharomyces cerevisiae, an important model fungus. Growth inhibition assays showed that Fe3O4 nanoparticles remarkably inhibited yeast growth. Interestingly, this inhibitory effect was not attributed to the well-known plasma membrane damage, cell wall damage and ROS accumulation. Further investigations revealed that the nanoparticles strongly impaired mitochondrial functions, resulting in abnormal mitochondrial morphology, decreased mitochondrial membrane potential (MMP) and attenuated ATP production. Most importantly, the respiratory chain complex Ⅳ, rather than other respiratory chain complexes and ATP synthases, was found to be the main target of the nanoparticles. This study uncovers a novel ROS-independent toxicity mechanism of Fe3O4 nanoparticles to eukaryotic cells.