Intestinal mitochondrial unfolded protein response induced by nanoplastic particles in Caenorhabditis elegans

In organisms, activation of mitochondrial unfolded protein response (mt UPR) provides the protective strategy against toxicity of environmental exposures. The aim of this study was to determine the activation of intestinal mt UPR and the underlying mechanisms in nanopolystyrene (100 nm) exposed Caenorhabditis elegans. The exposure was performed from L1-larvae for approximately 6.5-day. Activation of mt UPR as reflected by expressions of both HSP-6::GFP and hsp-6 in the intestine could be detected in nanopolystyrene (1-100 μg/L) exposed nematodes. Meanwhile, the susceptibility to nanoplastic toxicity was observed in hsp-6(RNAi) nematodes, suggesting the protective function of intestinal activation of mt UPR. After nanoplastic exposure, the activation of intestinal mt UPR was due to increase in expressions of ATFS-1, UBL-5, and DVE-1. Moreover, the activations of intestinal mt UPR mediated by ATFS-1, DVE-1, and UBL-5 was under the control of ELT-2 signaling, Wnt signaling, and insulin signaling, respectively. In the intestine, UBL-5, DVE-1, and ATFS-1 functioned in different pathways to control nanoplastic toxicity. Therefore, we provide an important molecular network of mt UPR activation in intestine of nematodes against the nanoplastic toxicity. Our findings highlight the importance of mt UPR activation in mediating a protective response to nanoplastics at low concentrations in organisms.