Nickel oxide nanoparticles trigger caspase- and mitochondria-dependent apoptosis in the yeast Saccharomyces cerevisiae

Abstract

The expansion of industrial use of nickel oxide (NiO) nanoparticles (NPs) raises concerns about their potential adverse effects. The present work aimed to investigate the mechanisms of toxicity induced by NiO NPs, using the yeast Saccharomyces cerevisiae, as cell model. Yeast cells exposed to NiO NPs exhibited typical hallmarks of regulated cell death (RCD) by apoptosis [loss of cell proliferation capacity (cell viability), exposure of phosphatidylserine at the outer cytoplasmic membrane leaflet, nuclear chromatin condensation and DNA damage] in a process which required de novo protein synthesis. The execution of yeast cell death induced by NiO NPs is Yca1p metacaspase-dependent. NiO NPs also induced the reduction of the mitochondrial membrane potential and the increase of the frequency of respiratory deficient mutants, which supports the involvement of mitochondria in the cell death process. Cells deficient in the apoptosis-inducing factor (aif1) displayed higher tolerance to NiO NPs, which reinforces the involvement of mitochondria in the RCD by apoptosis. In resume, this study shows that NiO NPs induce caspase- and mitochondria-dependent apoptosis in yeast. The presented results warn to the possible harmful effects associated with the use of NiO NPs.