Journal
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
Volume 235, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2022.113438
Keywords
Copper; Mitochondria-associated endoplasmic; reticulum membrane (MAM); Autophagy; Mitofusin2; Kidney
Categories
Funding
- National Natural Science Founda-tion of China [31902333]
- Jiangxi Provincial Natural Science Foundation [20212BAB215017]
- Science and Technology Plan of Education Department of Jiangxi Province [GJJ190216]
Ask authors/readers for more resources
This study revealed the interaction between Mfn2-dependent MAM dynamics and autophagy in duck renal tubular epithelial cells under Cu exposure. Excessive Cu disrupted MAM integrity and activated autophagy.
Copper (Cu) as a transition metal can be toxic to public and ecosystem health at high level, but the specific mechanism of Cu-evoked nephrotoxicity remains elusive. Here, we first revealed the crosstalk between mito-fusin2 (Mfn2)-dependent mitochondria-associated endoplasmic reticulum membrane (MAM) dynamics and autophagy in duck renal tubular epithelial cells under Cu exposure. Primary duck renal tubular epithelial cells were treated with 100 and 200 mu M Cu sulfate for 12 h and exposed to lentivirus to deliver mitofusin2 (Mfn2). We found that excessive Cu disrupted MAM integrity, decreased the mitochondrial calcium level, co-localization of IP3R and VDAC1, the mRNA levels of PACS2, Mfn2, IP3R and MCU, and Mfn2 and VDAC1 protein levels, causing MAM dysfunction. Furthermore, Mfn2 overexpression ameliorated Cu-induced MAM dysfunction, and increased Cu-evoked autophagy in duck renal tubular epithelial cells accompanied with the elevation of autophagosomes number, ROS level, LC3 puncta, Atg5 and LC3B mRNA levels, and Beclin1, Atg14, LC3BII/LC3BI protein levels. Accordingly, our data proved that excessive Cu could trigger MAM dysfunction and autophagy in duck renal tubular epithelial cells, and Cu-induced autophagy could be activated through Mfn2-dependent MAM, providing evidence on the toxicological exploration mechanisms of Cu.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available