Prion-induced ferroptosis is facilitated by RAC3.

ABSTRACT: Prions are infectious agents that initiate transmissible spongiform encephalopathies, causing devastating neuronal destruction in Creutzfeldt-Jakob and Kuru disease. Rapid cell death depends on presence of the endogenous prion protein PrP^C, but its mechanistic contribution to pathogenesis is unclear. Here we investigate the molecular role of PrP^C, reactive oxygen species and lipid metabolism in ferroptosis susceptibility, a regulated cell death process characterized by lipid peroxidation. We discover that elevated expression of the cellular prion PrP^C creates a relaxed oxidative milieu that favors accumulation of unsaturated long-chain phospholipids responsible for ferroptotic death. This condition is sustained by the luminal protein glutathione peroxidase

SUBMITTER: Peng H 

PROVIDER: S-EPMC12198409 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature