Superoxide Activates Ferroptosis via the Haber-Weiss Reaction and Enhances Age-Related Macular Degeneration.

Antioxidant decline is crucial to driving age-related macular degeneration (AMD). Ferroptosis, a regulated cell death mediated by iron-dependent hydroxyl radical-catalyzed phospholipid peroxidation through the Fenton reaction, is implicated in various chronic degenerative diseases. Here, we show that superoxide activates ferroptosis in retinal pigment epithelium (RPE) cells via the Haber-Weiss reaction, thereby contributing to dry AMD.

Identification of the central role of RNA polymerase mitochondrial for angiogenesis.

Mitochondria are central to endothelial cell activation and angiogenesis, with the RNA polymerase mitochondrial (POLRMT) serving as a key protein in regulating mitochondrial transcription and oxidative phosphorylation. In our study, we examined the impact of POLRMT on angiogenesis and found that its silencing or knockout (KO) in human umbilical vein endothelial cells (HUVECs) and other endothelial cells resulted in robust anti-angiogenic effects, impeding cell proliferation, migration, and capillary tube formation. Depletion of POLRMT led to impaired mitochondrial function, characterized by mitochondrial depolarization, oxidative stress, lipid oxidation, DNA damage, and reduced ATP production, along with significant apoptosis activation.