CHAC1 as a Novel Contributor of Ferroptosis in Retinal Pigment Epithelial Cells with Oxidative Damage.
Ye LiuDi WuQiuli FuShengjie HaoYuzhou GuWei ZhaoShuying ChenFeiyin ShengYili XuZhiqing ChenKe YaoPublished in: International journal of molecular sciences (2023)
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 2+ 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.
Keyphrases
- cell death
- age related macular degeneration
- induced apoptosis
- cell cycle arrest
- oxidative stress
- endoplasmic reticulum stress
- single cell
- optical coherence tomography
- dna damage
- diabetic retinopathy
- fatty acid
- ischemia reperfusion injury
- gene expression
- dna methylation
- risk assessment
- climate change
- cell proliferation
- human health
- protein protein
- heat shock