Mitochondria-associated endoplasmic reticulum membranes participate mitochondrial dysfunction and endoplasmic reticulum stress caused by copper in duck kidney.

Copper (Cu) can be harmful to host physiology at high levels, although it is still unclear exactly how it causes nephrotoxicity. Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are associated with heavy metal intoxication. Meanwhile, mitochondria and ER are connected via mitochondria-associated ER membranes (MAM). In order to reveal the crosstalk between them, a total of 144 1-day-old Peking ducks were randomly divided into four groups: control (basal diet), 100 mg/kg Cu, 200 mg/kg Cu, and 400 mg/kg Cu groups. Results found that excessive Cu disrupted MAM integrity, reduced the co-localization of IP3R and VDAC1, and significantly changed the MAM-related factors levels (Grp75, Mfn2, IP3R, MCU, PACS2, and VDAC1), leading to MAM dysfunction. We further found that Cu exposure induced mitochondrial dysfunction via decreasing the ATP level and the expression levels of COX4, TOM20, SIRT1, and OPA1 and up-regulating Parkin expression level. Meanwhile, Cu exposure dramatically increased the expression levels of Grp78, CRT, and ATF4, resulting in ER stress. Overall, these findings demonstrated MAM plays the critical role in Cu-induced kidney mitochondrial dysfunction and ER stress, which deepened our understanding of Cu-induced nephrotoxicity. © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Citation

Junjun Peng, Xueyan Dai, Huiqin Fan, Chenghong Xing, Yu Zhuang, Xiaona Gao, Huabin Cao, Guoliang Hu, Fan Yang. Mitochondria-associated endoplasmic reticulum membranes participate mitochondrial dysfunction and endoplasmic reticulum stress caused by copper in duck kidney. Environmental science and pollution research international. 2023 Jul;30(31):77127-77138

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PMID: 37253910

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