Perturbation of calcium homeostasis and multixenobiotic resistance by nanoplastics in the ciliate Tetrahymena thermophila

Microplastics (MPs) are an environmental hazard of growing concern, including their potential toxic effects on the biota of different trophic levels. Nevertheless, the molecular mechanisms underlying MP-induced toxicity remain largely unknown. In the present study, Tetrahymena thermophila was exposed to polystyrene nanoplastics (PS-NPs) and the responses of this relatively sensitive ciliate were then followed using transcriptome analysis together with several other verification methods. The results showed that PS-NPs perturbed calcium (Ca) homeostasis, by inducing the inositol-1,4,5-trisphosphate-dependent liberation of Ca from the endoplasmic reticulum into the cytosol. The high cytosolic concentration of Ca induced Ca accumulation in mitochondria, which increased mitochondrial permeability and the generation of reactive oxygen species, finally leading to growth inhibition. Such toxicity is the so-called direct effects of PS-NPs. By contrast, PS-NPs also inhibited the activity of multixenobiotic resistance transporter, by down-regulating the ATP-binding cassette transporter genes Abcb15 and Abcc52. This additional effect may alter cellular responses to other pollutants and implicates PS-NPs in the risks to the organism posed by subsequent toxic exposures, which was named as the indirect effects of PS-NPs. Our study highlights the importance of considering both direct and indirect biological effects of MPs in evaluations of their environmental and health risks.