Effects of CuSO₄ on hepatic mitochondrial function, biogenesis and dynamics in mice

Copper is an essential trace element for animal. Excessive intake of copper will cause a large accumulation of copper in the body, especially in the liver, and induce hepatotoxicity, however, there are few studies on the effects of copper on hepatic mitochondrial biogenesis and mitochondrial dynamics. In this study, mice were treated with different doses of CuSO₄ (0, 10, 20, and 40 mg/kg) for 21 and 42 days by gavage. The results verified that CuSO₄ decreased the content of mitochondrial respiratory chain complexes I-IV in mouse liver. CuSO₄ treatment resulted the decrease in the protein and mRNA expression levels of PGC-1α, TFAM, and NRF1, which were the mitochondrial biogenesis regulator proteins. Meanwhile, the proteins involved in mitochondrial fusion were reduced by CuSO₄ , such as Mfn1 and Mfn2, however, mitochondrial fission proteins Drip1 and Fis1 were significantly increased. Abovementioned results show that CuSO₄ could induce mitochondria damage in the liver of mice, and mitochondrial biogenesis and mitochondrial dynamics are involved in the molecular mechanism of CuSO₄ -induced hepatotoxicity.