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

• Published in: International journal of molecular sciences Vol. 24; no. 2; p. 1582
• Main Authors: Liu, Ye, Wu, Di, Fu, Qiuli, Hao, Shengjie, Gu, Yuzhou, Zhao, Wei, Chen, Shuying, Sheng, Feiyin, Xu, Yili, Chen, Zhiqing, Yao, Ke
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13-01-2023; MDPI
• Subjects: age-related macular degeneration (AMD); Aged; Aging; Apoptosis; Biological effects; Cells; Chac1; Depletion; Environmental stress; Epithelial Cells - metabolism; Epithelium; Ferroptosis; Ferroptosis - genetics; Ferroptosis - physiology; Gene expression; Geriatrics; Glutathione - metabolism; Humans; Hydrogen peroxide; Iron; Lasers; Lipid peroxidation; Lipids; Macular degeneration; Macular Degeneration - metabolism; Metabolism; Molecular modelling; Oxidative stress; Oxidative Stress - genetics; Oxidative Stress - physiology; Pathogenesis; Protein folding; Proteins; Retina; Retinal degeneration; retinal pigment epithelial (RPE); Retinal pigment epithelium; Retinal Pigment Epithelium - metabolism; Retinal Pigments - metabolism; γ-Glutamylcyclotransferase; Chac1; age-related macular degeneration (AMD); ferroptosis; retinal pigment epithelial (RPE); oxidative stress
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24021582

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 Fe
accumulation and lipid peroxidation in RPE cells. Glutathione specific gamma-glutamylcyclotransferase 1 (
), 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
as a novel contributor of oxidative-stress-induced ferroptosis in RPE, suggesting its potential role in AMD.