Mn3O4 nanoparticles cause endoplasmic reticulum stress-dependent toxicity to Saccharomyces cerevisiae

Abstract

Mn₃O₄ nanoparticles (NPs) are a significant nanomaterial (NM) due to their excellent physiochemical properties. However, little is known about their biological effects. In this study, we investigated the effect of the synthesized Mn₃O₄ nanoparticles (NPs) (with the size of 10–25 nm) on the important fungus model, Saccharomyces cerevisiae. Growth inhibition assays showed that Mn₃O₄ NPs had dose-dependent toxicity to Saccharomyces cerevisiae (IC₅₀ = 340 ppm). The plasma membrane (PM) was not damaged by the NPs, and the addition of ROS scavengers could not attenuate growth inhibition of the NPs to yeast cells, ruling out the contribution of PM damage and oxidative stress to this toxicity. Interestingly, Mn₃O₄ NPs caused HAC1 mRNA splicing and remarkable up-regulation of the unfolded protein response (UPR) genes, indicating that the NPs induce severe endoplasmic reticulum (ER) stress. Moreover, treatment of the NPs severely reduced the activity of both extracellular invertase and surface ferric reductase, which might be attributable to ER stress-related disruption of the secretion pathway. This study uncovers a novel toxicity mechanism of Mn₃O₄ NPs against eukaryotic cells, and provides useful information for assessing the environmental impact of NMs.