CHAC1 as a Novel Contributor of Ferroptosis in Retinal Pigment Epithelial Cells with Oxidative Damage

作者：Ye Liu, Di Wu, Qiuli Fu, Shengjie Hao, Yuzhou Gu, Wei Zhao, Shuying Chen, Feiyin Sheng, Yili Xu, Zhiqing Chen, Ke Yao · 发表于：International Journal of Molecular Sciences · 年份：2023 · DOI：10.3390/ijms24021582 · 被引用次数：54 · 研究领域：Ferroptosis and cancer prognosis、Connexins and lens biology、Heme Oxygenase-1 and Carbon Monoxide

Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly population. With aging and the accumulated effects of environmental stress, retinal pigment epithelial (RPE) cells are particularly susceptible to oxidative damage, which can lead to retinal degeneration. However, the underlying molecular mechanisms of how RPE responds and progresses under oxidative damage are still largely unknown. Here, we reveal that exogenous oxidative stress led to ferroptosis characterized by Fe2+ accumulation and lipid peroxidation in RPE cells. Glutathione specific gamma-glutamylcyclotransferase 1 (Chac1), as a component of the unfolded protein response (UPR) pathway, plays a pivotal role in oxidative-stress-induced cell ferroptosis via the regulation of glutathione depletion. These results indicate the biological significance of Chac1 as a novel contributor of oxidative-stress-induced ferroptosis in RPE, suggesting its potential role in AMD.