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

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Abstract

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.

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Data availability

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

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Funding

This research was funded by the National Natural Science Foundation of China (No. 31902333), Jiangxi Provincial Natural Science Foundation (20212BAB215017), and Science and Technology Plan of Education Department of Jiangxi Province (GJJ190216).

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  1. Junjun Peng and Xueyan Dai contributed equally to this work.

Authors and Affiliations

  1. Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Economic and Technological Development District, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Nanchang, 330045, Jiangxi, People’s Republic of China

    Junjun Peng, Xueyan Dai, Huiqin Fan, Chenghong Xing, Yu Zhuang, Xiaona Gao, Huabin Cao, Guoliang Hu & Fan Yang

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  1. Junjun Peng
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Contributions

All authors contributed to the study conception and design. Junjun Peng: methodology, formal analysis, investigation, visualization, and writing—original draft. Xueyan Dai: data curation, formal analysis, investigation, and writing—review and editing. Huiqin Fan and Chenghong Xing: methodology and investigation. Yu Zhuang and Xiaona Gao: investigation, formal analysis, and visualization. Huabin Cao and Guoliang Hu: resources, supervision, and methodology. Fan Yang: conceptualization, supervision, project administration, and funding acquisition. All authors have read the manuscript and agreed to submit it in its current form for consideration for publication in the Journal.

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Correspondence to Fan Yang.

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Peng, J., Dai, X., Fan, H. et al. Mitochondria-associated endoplasmic reticulum membranes participate mitochondrial dysfunction and endoplasmic reticulum stress caused by copper in duck kidney. Environ Sci Pollut Res 30, 77127–77138 (2023). https://doi.org/10.1007/s11356-023-27924-z

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