Naringin reduces mitochondrial fragmentation and excessive mitophagy in cerebral ischemia-reperfusion injury via the S-nitrosylated Dynamin-related protein 1 (SNO-DRP1) / Leucine-rich repeat kinase 2 (LRRK2) / Mitochondrial Calcium Uniporter (MCU) pathway

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BACKGROUND: . PURPOSE: This study aimed to examine the influence of the S-nitrosylated dynamin-related protein 1 (SNO-DRP1)/leucine-rich repeat kinase 2 (LRRK2)/mitochondrial calcium uniporter (MCU) pathway on harmful mitophagy, which is inhibited by naringin in CI/R injury. METHODS: fluorescence intensity following Rhod-2 AM treatment, and assessing the opening of the mitochondrial permeability transition pore. The mitochondrial reactive oxygen species and mitochondrial DNA release were used to evaluate the mitochondrial endosymbiosis failure. RESULTS: overload and mitochondrial endosymbiosis disruption. Notably, only SIN-1 reversed naringin's suppression of SNO-DRP1 formation and its interaction with LRRK2 in vitro. CONCLUSIONS: This study demonstrates that naringin reduces ONOO⁻-caused harmful mitophagy in CI/R injury by blocking the SNO-DRP1/LRRK2/MCU pathway, which helps prevent mitochondrial fragmentation and preserve mitochondrial endosymbiosis. This pathway may be among the mechanisms by which naringin exerts its protective effects.