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Two mTOR inhibitors, rapamycin and Torin 1, differentially regulate iron-induced generation of mitochondrial ROS

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Abstract

It is generally believed that gene-environment interaction may contribute to neurodegeneration. Of particular note is that iron overload may be one of the risk factors for neurodegeneration. However, the mechanisms underlying iron-associated neurotoxicity are not fully understood. Here we explored the effects of mechanistic target of rapamycin (mTOR) inhibition in iron-stressed human neuroblastoma cells. Two mTOR inhibitors, rapamycin and Torin 1, had similar effects in cells exposed to a relatively low concentration of iron. At a higher concentration of iron, Torin 1, instead of rapamycin, could further aggravate iron-induced cytotoxicity, and mitochondrial ROS levels were significantly higher in Torin 1-treated cells. These results suggest that mTOR inhibition may not be able to alleviate iron-induced neurotoxicity.

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Acknowledgements

We acknowledge the financial support from National Natural Science Foundation of China (Grant No. 11375213, 21390411), the Hundred Talents Program of the Chinese Academy of Sciences and IHEP Innovation Program.

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Correspondence to Yi Hu.

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Huang, H., Chen, J., Lu, H. et al. Two mTOR inhibitors, rapamycin and Torin 1, differentially regulate iron-induced generation of mitochondrial ROS. Biometals 30, 975–980 (2017). https://doi.org/10.1007/s10534-017-0059-1

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  • DOI: https://doi.org/10.1007/s10534-017-0059-1

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