Exposure to copper and copper-based nanoparticles induces hepatopancreatic mitochondrial dysfunction by triggering mtROS mediated apoptosis and mitophagy in Eriocheir sinensis.

Copper (Cu) is an important metal pollutant commonly found in aquatic environment owing to its inherent bioaccumulation and biomagnification potentials and long-term persistence in environmental compartments. The application of novel fabricated copper nanoparticles (Cu-NPs) has led to cytotoxicity in aquatic animals. However, the differences in underlying toxicity mechanisms between Cu-NPs and waterborne Cu (such as CuSO) remain unelucidated. Herein, the mechanisms underlying the CuSO/Cu-NPs-mediated perturbation of the hepatopancreatic mitochondrial function at different concentrations were investigated and compared. After exposing Eriocheir sinensis to 0 (control), 5, 50, and 500 μg/L CuSO and 10 μg/L Cu-NPs for 21 days, hepatopancreases were retrieved. The results revealed that Cu-NPs or CuSO (50 and 500 μg/L) induced ultrastructural damage following a time-dose effect, as indicated by swelling and degeneration of the lumen of hepatic tubules. Excess CuSO or Cu-NPs exposure decreased the antioxidative capacity and led to the over-accumulation of mitochondrial ROS. Moreover, the mitochondrial membrane potential (ΔΨm) was reduced and apoptosis induced. Additionally, both CuSO and Cu-NPs increased the numbers of mitophagosomes and the mRNA and protein levels of LC3B, and triggered mitophagy through PRKN-independent pathway; however, mostly the BNIP3L/Beclin1 pathway was involved in excess CuSO-induced mitophagy. Altogether, this study provides a basis for exploring Cu-mediated potential mitochondrial autophagy activation mechanisms and their effects on environmental toxicity.