SKN-1/Nrf2-dependent regulation of mitochondrial homeostasis modulates transgenerational toxicity induced by nanoplastics with different surface charges in Caenorhabditis elegans

• DOI: 10.1016/j.jhazmat.2023.131840
• Publication Date: 2023-06-13T06:43:34Z
• Authors: Man Qu; Long Miao; He Chen; Xing Zhang; Yang Wang
• Keywords: NF-E2-Related Factor 2; Microplastics; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Mitochondria

The toxic effects of nanoplastics on transgenerational toxicity in environmental organisms and the involved mechanisms remain poorly comprehended. This study aimed to identify the role of SKN-1/Nrf2-dependent regulation of mitochondrial homeostasis in response to transgenerational toxicity caused by changes in nanoplastic surface charges in Caenorhabditis elegans (C. elegans). Our results revealed that compared with the wild-type control and PS exposed groups, exposure to PS-NH2 or PS-SOOOH at environmentally relevant concentrations (ERC) of ≥ 1 μg/L caused transgenerational reproductive toxicity, inhibited mitochondrial unfolded protein responses (UPR) by downregulating the transcription levels of hsp-6, ubl-5, dve-1, atfs-1, haf-1, and clpp-1, membrane potential by downregulating phb-1 and phb-2, and promoted mitochondrial apoptosis by downregulating ced-4 and ced-3 and upregulating ced-9, DNA damage by upregulating hus-1, cep-1, egl-1, reactive oxygen species (ROS) by upregulating nduf-7 and nuo-6, ultimately resulting in mitochondrial homeostasis. Additionally, further study indicated that SKN-1/Nrf2 mediated antioxidant response to alleviate PS-induced toxicity in the P0 generation and dysregulated mitochondrial homeostasis to enhance PS-NH2 or PS-SOOOH-induced transgenerational toxicity. Our study highlights the momentous role of SKN-1/Nrf2 mediated mitochondrial homeostasis in the response to nanoplastics caused transgenerational toxicity in environmental organisms.