Increased Mobile Zinc Regulates Retinal Ganglion Cell Survival via Activating Mitochondrial OMA1 and Integrated Stress Response.

ABSTRACT: Retinal ganglion cells (RGCs), the projection neurons of the eye, are irreversibly lost once the optic nerve is injured, which is a critical mechanism of glaucoma. Mobile zinc (Zn²⁺) levels rapidly increase in retinal interneuron amacrine cells and Zn²⁺ is then transferred to RGCs via the Zn²⁺ transporter protein ZnT-3, triggering RGC loss in optic nerve injury. Zn²⁺ chelation and ZnT-3 deletion promote long-term RGC survival. However, the downstream signaling pathways of Zn²⁺ in RGCs remains unknown. Here, we show that increased levels of Zn²⁺ upregulate the expression and activity of mitochondrial zinc metallopeptidase OMA1 in the retina, leading to the cleavage of DELE1 and activation of cytosolic eIF2α kinase PKR, trigge

SUBMITTER: Tang J 

PROVIDER: S-EPMC9598227 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature