posted on 2024-07-10, 20:09authored byQuanwei Li, Pan Guo, Shaofeng Wang, Luna Su, Wenlan Yu, Jianying Guo, Liammei Hu, Hui Zhang, Jiaqiang Pan, Zhaoxin Tang, Jianzhao Liao
As an efficient alternative copper (Cu) source, copper
nanoparticles
(nano-Cu) have been widely supplemented into animal-producing food.
Therefore, it is necessary to assess the effect of nano-Cu exposure
on the biological health risk. Recently, the toxic effects of nano-Cu
have been confirmed but the underlying mechanism remains unclear.
This study reveals the impact of nano-Cu on endoplasmic reticulum
autophagy (ER-phagy) in chicken hepatocytes and further identifies
Drp1 and its downstream gene FAM134B as crucial regulators of nano-Cu-induced
hepatotoxicity. Nano-Cu exposure can induce Cu ion overaccumulation
and pathological injury in the liver, trigger excessive mitochondrial
fission and mitochondria-associated membrane (MAM) integrity damage,
and activate ER-phagy in vivo and in vitro. Interestingly, the knockdown
of Drp1 markedly decreases the expression of FAM134B induced by nano-Cu.
Furthermore, the expression levels of ATL3, CCPG1, SEC62, TEX264,
and LC3II/LC3I induced by nano-Cu exposure are decreased by inhibiting
the expression of Drp1. Simultaneously, the inhibition of FAM134B
effectively alleviates nano-Cu-induced ER-phagy by downregulating
the expression of ATL3, CCPG1, SEC62, TEX264, and LC3II/LC3I. Overall,
these results suggest that Drp1-mediated impairment of MAM integrity
leads to ER-phagy as a novel molecular mechanism involved in the regulation
of nano-Cu-induced hepatotoxicity. These findings provide new ideas
for future research on the mechanism of nano-Cu-induced hepatotoxicity.