Mitophagy: a regulator and therapeutic target in cerebral ischemia/reperfusion injury.
TL;DR
This review summarizes the molecular regulation of mitophagy, its role in cerebral I/R injury, and current therapeutic strategies aimed at modulating mitophagy for maintaining mitochondrial homeostasis in cerebral I/R injury treatment.
Abstract
Cerebral ischemia/reperfusion (I/R) injury refers to the exacerbation of tissue damage following the restoration of blood flow to ischemic brain regions. This condition remains a major challenge in the clinical management of ischemic stroke due to limited therapeutic options. At present, no approved drugs specifically target cerebral I/R injury. Multiple mechanisms contribute to its pathogenesis, with mitochondrial dysfunction playing a central role. During cerebral I/R injury, mitochondria generate excessive reactive oxygen species (ROS), leading to impaired mitochondrial function and further tissue damage. In addition, mitochondrial calcium overload triggers neuronal apoptosis, which promotes disease progression. Given the critical role of mitochondrial dysfunction, preservation of mitochondrial homeostasis may attenuate cerebral I/R injury. Mitophagy, a selective process that removes damaged mitochondria, has been shown to mitigate cerebral I/R injury by limiting the release of harmful mitochondrial-derived factors. Therefore, mitophagy represents a potential therapeutic target for maintaining mitochondrial homeostasis in cerebral I/R injury treatment. This review summarizes the molecular regulation of mitophagy, its role in cerebral I/R injury, and current therapeutic strategies aimed at modulating mitophagy.