Syntaxin 17 Translocation Mediated Mitophagy Switching Drives Hyperglycemia-Induced Vascular Injury

文献类型： 外文期刊

第一作者： Luo, Anqi

作者： Luo, Anqi;Liu, Xiaoquan;Liu, Haochen;Wang, Rui;Zheng, Yunsi;Gong, Jingwen;Wang, Shuting;Yun, Chuan;Chen, Zongcun;Jiang, Yanan;Dai, Haofu

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关键词： (diabetes; Fis1; mitophagy; Syntaxin 17); vascular endothelial injury

期刊名称：ADVANCED SCIENCE （ 影响因子：14.1； 五年影响因子：15.6 ）

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年卷期： 2025 年 12 卷 19 期

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收录情况： SCI

摘要： The risk of diabetic cardiovascular complications is closely linked to the length of hyperglycemia exposure. Mitophagy plays a significant role in vascular endothelial injury. However, the specific mechanisms by which mitophagy contributes to endothelial injury during sustained hyperglycemia remain unclear. In diabetic ApoE(-/- )mice and human umbilical vein endothelial cell (HUVEC) models, mitophagy is enhanced following short-term and long-term high-glucose exposure. Short-term high-glucose exposure promotes Parkin-mediated mitophagy and upregulates mitochondrial fission protein 1 (Fis1) expression, whereas long-term high-glucose exposure suppresses Parkin-mediated mitophagy and downregulates Fis1. With prolonged high-glucose exposure, Syntaxin 17 (STX17) translocates from the endoplasmic reticulum to the mitochondria, activating STX17-mediated mitophagy. Silencing STX17 alleviates mitochondrial degradation, decreases reactive oxygen species (ROS) levels, enhances endothelial nitric oxide synthase (eNOS) phosphorylation, and reduces apoptosis. Silencing Fis1 accelerates the switching to STX17-mediated mitophagy, worsening endothelial dysfunction, whereas Fis1 overexpression prevents this switching, reducing ROS and apoptosis and enhancing eNOS phosphorylation. In summary, these findings suggest that the switching from Parkin-mediated to STX17-mediated mitophagy drives vascular endothelial injury following long-term hyperglycemic exposure, providing valuable insights into therapeutic strategies for diabetic cardiovascular complications.

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