Extracellular vesicle-mediated delivery of mitochondrial circRNA MTCO2 protects against cerebral ischemia by modulating mPTP-dependent ferroptosis.

ABSTRACT: Ischemic stroke remains a major cause of mortality and long-term disability, with few effective neuroprotective treatments currently available. Ferroptosis, an iron-dependent form of regulated cell death marked by lipid peroxidation, is increasingly recognized as a driver of neuronal damage. However, the mitochondrial mechanisms linking ischemia to ferroptosis remain poorly defined. Here, we identify circMTCO2, a mitochondria-encoded circular RNA, as a novel endogenous modulator of neuronal ferroptosis. CircMTCO2 expression is dynamically downregulated following cerebral ischemia/reperfusion both in vitro and in vivo. Mechanistically, circMTCO2 binds directly to adenine nucleotide translocase 1 (ANT1), a key component of the mitochondrial permeability transition pore (mPTP), thereby inhibi

SUBMITTER: Yang J 

PROVIDER: S-EPMC12344986 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature