Polystyrene nanoparticles cause dynamic alteration in mitochondrial unfolded protein response from parents to the...

The mitochondrial unfolded protein response (mt UPR) is important for organisms against the toxicity from toxicants and stresses. Polystyrene nanoparticle (PS-NP), one of the emerging pollutants, has aroused increasing concern for its toxicity in the offspring. Nevertheless, the molecular basis for this transgenerational toxicity remains largely unclear. In this study, the role of mt UPR in the induction of transgenerational toxicity was determined in Caenorhabditis elegans (C. elegans) after parental exposure to PS-NP. After exposure to PS-NP (1-100 μg/L), the suppression in mt UPR showed the concentration-dependent in nematodes from P0 generation (P0-G) to F2-G. Moreover, the decreased expression of genes required for controlling mt UPR (atfs-1, dve-1, and ubl-5 genes) were observed from P0-G to F2-G after exposure to PS-NP (1 μg/L). The adverse effects on locomotion and reproductive capacity were more severe over generations in nematodes with RNAi of these three genes, indicating that these genes were involved in controlling transgenerational toxicity. After parental PS-NP exposure (1 μg/L), the mt UPR was significantly inhibited by RNAi of atfs-1, dve-1, and ubl-5, indicating the association between the transgenerational PS-NP toxicity and mt UPR suppression. Additionally, during the transgenerational process, RNAi of atfs-1, dve-1, and ubl-5 enhanced the PS-NP toxicity by suppressing mt UPR, while RNAi of daf-2 encoding an insulin receptor inhibited the PS-NP toxicity by increasing mt UPR. Therefore, our data highlighted the role of inhibition in mt UPR in mediating the transgenerational nanoplastic toxicity in nematodes.