Lysosome DMT1-Mediated Renal Cell Ferroptosis Induced by Ochratoxin A
Qian Lin, Tongle Zhou, Yujun Tan, Famous Erhunmwunsee, Ruhui Wang, Zhida Zhao, Chen Fan, Hongxia Ren, Xue Peng, Jun Tian, Man LiuAbstract
The mycotoxin ochratoxin A (OTA) was reported to induce ferroptosis in renal cells, but the role of lysosomal DMT1 remained unclear. In the current study, the induction of ferroptosis was first determined by assessments of cell viability, mitochondrial phenotypes, Fe2+ content, and lipid peroxidation levels in NRK-52E and 293T cells. At both mRNA and protein expression levels, OTA exposure resulted in an increase in DMT1 levels. Interestingly, lysosomes were found to colocalize with Fe2+ upon exposure to OTA. Lysosome inhibitor BafA1 reduced OTA-induced ferroptosis and activation of DMT1 and FTH. Additionally, OTA treatment resulted in the rapid movement of DMT1 to lysosomes by quantifying the colocalization of pEGFP-N1-DMT1 and lysosome tracker. Silencing of DMT1 reversed OTA-induced cell death and lipid peroxidation. Collectively, this study elucidates the critical role of lysosome-dependent DMT1 in the ferroptosis of renal cells induced by OTA, offering a comprehensive strategy for mitigating the OTA-induced nephrotoxicity.