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SKN-1/Nrf2-dependent regulation of mitochondrial homeostasis modulates transgenerational toxicity induced by nanoplastics with different surface charges in Caenorhabditis elegans
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Researchers found that nanoplastics with different surface charges caused reproductive toxicity that persisted across multiple generations in the roundworm C. elegans. Positively and negatively charged nanoplastics disrupted mitochondrial function through a stress-response pathway called SKN-1/Nrf2, with effects lasting even in unexposed offspring. This suggests that nanoplastic exposure could have lasting biological consequences that extend beyond the directly exposed generation.
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-NH 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-NH 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.
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