Work

Oxyglutamate Carrier Alleviates Cerebral Ischaemia–Reperfusion Injury by Regulating Mitochondrial Function

Year: 2025

Type: article

Abstract: Mitochondrial dysfunction has been reported to participate in the pathophysiological processes of cerebral ischaemia-reperfusion injury, which include reduced energy homeostasis, increased generation of oxidative stress species (ROS) and the release of apoptotic factors. Oxyglutamate carrier (OGC) is an important carrier protein on the inner mitochondrial membrane that can transport metabolites from the cytoplasm to the mitochondria. The role of OGC in cerebral ischaemia-reperfusion injury (I/R) remains unknown. In this study, we found that the expression of OGC was significantly upregulated after cerebral ischaemia-reperfusion injury. Inhibiting OGC with phenylsuccinic acid (PSA) increased neuronal death after oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Mechanistically, OGC was localized in mitochondria and could facilitate the transport of glutathione from the cytoplasm to the mitochondria to reduce ROS levels and increase ATP production after OGD/R. In addition, in vivo inhibition of OGC exacerbated brain infarction, and GSH supplementation alleviated brain infarction resulting from OGC inhibition. This study revealed the role of OGC in alleviating brain damage by regulating mitochondrial GSH transport to alleviate mitochondrial function after cerebral ischaemia-reperfusion injury, which may provide a target for alleviating ischaemic brain injury.

Source: European Journal of Neuroscience

DOI: 10.1111/ejn.16659