Li-Kai Chu, Xu Cao, Lin Wan, Qiang Diao, Yu Zhu, Yu Kan, Li-Li Ye, Yi-Ming Mao, Xing-Qiang Dong, Qian-Wei Xiong, Ming-Cui Fu, Ting Zhang, Hui-Ting Zhou, Shi-Zhong Cai, Zhou-Rui Ma, Ssu-Wei Hsu, Reen Wu, Ching-Hsien Chen, Xiang-Ming Yan, Jun Liu
Ferroptosis is an iron-dependent programmed cell death associated with severe kidney diseases, linked to decreased glutathione peroxidase 4 (GPX4). However, the spatial distribution of renal GPX4-mediated ferroptosis and the molecular events causing GPX4 reduction during ischemia-reperfusion (I/R) remain largely unknown. Using spatial transcriptomics, we identify that GPX4 is situated at the interface of the inner cortex and outer medulla, a hyperactive ferroptosis site post-I/R injury. We further discover OTU deubiquitinase 5 (OTUD5) as a GPX4-binding protein that confers ferroptosis resistance by stabilizing GPX4...
December 18, 2023: Nature Communications