Cdk5-mediated Drp1 phosphorylation drives mitochondrial defects and neuronal apoptosis in radiation-induced optic neuropathy.

ABSTRACT: Radiation-induced optic neuropathy (RION) is a devastating complication following external beam radiation therapy (EBRT) that leads to acute vision loss. To date, no efficient, available treatment for this complication, due partly to the lack of understanding regarding the developmental processes behind RION. Here, we report radiation caused changes in mitochondrial dynamics by regulating the mitochondrial fission proteins dynamin-related protein 1 (Drp1) and fission-1 (Fis1). Concurrent with an excessive production of reactive oxygen species (ROS), both neuronal injury and visual dysfunction resulted. Further, our findings delineate an important mechanism by which cyclin-dependent kinase 5 (Cdk5)-mediated phosphorylation of Drp1 (Ser616) regulates defects in mitochondrial dynamics associa

SUBMITTER: Rong R 

PROVIDER: S-EPMC7473761 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature