Zhu Hou-Wei, Wang Yi-Ping, Zhang Qiu-Fang, Wang Kai-Di, Huang Yan, Xiang Ruo-Lan
Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Xiamen Medical College, Xiamen Key Laboratory of Stomotalogical Disease Diagnosis and Treatment, Xiamen, China.
Xiamen Key Laboratory of Stomotalogical Disease Diagnosis and Treatment, Stomatological Hospital of Xiamen Medical College, Xiamen, China.
Oral Dis. 2024 Nov;30(8):5429-5444. doi: 10.1111/odi.14983. Epub 2024 May 12.
Diabetes is accompanied by a high prevalence of hyposalivation, causing severe damage to oral and systemic health. Mitochondrial dynamics play important roles in the pathogenesis of various diabetic complications; however, little is known about their roles in diabetic hyposalivation.
A diabetic mouse model and a high glucose (HG)-induced diabetic submandibular gland (SMG) cell model were employed.
More mitochondria surrounded by autophagosomes and higher expression of mitophagy-related proteins were detected in the SMGs of diabetic mice and HG-treated SMG cells. In diabetic SMGs, dynamin-related protein 1 (DRP1) was upregulated, whereas mitofusin-2 was downregulated both in vivo and in vitro. Shortened mitochondria and impaired mitochondrial functions were observed in the HG group. A DRP1-specific inhibitor, mdivi-1, suppressed mitochondrial fission and mitophagy, as well as restored mitochondrial functions in the HG condition. Moreover, the interaction of F-actin and DRP1 was enhanced in the diabetic group. Inhibiting F-actin with cytochalasin D repaired the injured effects of HG on mitochondrial dynamics and functions. Conversely, the F-actin-polymerization-inducer jasplakinolide aggravated mitochondrial fission and dysfunction.
F-actin contributes to HG-evoked mitochondrial fission by interacting with DRP1, which induces mitophagy and impairs mitochondrial function in SMG cells, ultimately damaging the SMG.
糖尿病常伴有高发性唾液分泌减少，对口腔和全身健康造成严重损害。线粒体动力学在各种糖尿病并发症的发病机制中起重要作用；然而，其在糖尿病性唾液分泌减少中的作用却鲜为人知。
采用糖尿病小鼠模型和高糖（HG）诱导的糖尿病下颌下腺（SMG）细胞模型。
在糖尿病小鼠的SMG和HG处理的SMG细胞中，检测到更多被自噬体包围的线粒体以及更高水平的线粒体自噬相关蛋白表达。在糖尿病SMG中，动力相关蛋白1（DRP1）上调，而线粒体融合蛋白2在体内和体外均下调。HG组观察到线粒体缩短和线粒体功能受损。DRP1特异性抑制剂mdivi-1可抑制线粒体分裂和线粒体自噬，并在HG条件下恢复线粒体功能。此外，糖尿病组中F-肌动蛋白与DRP1的相互作用增强。用细胞松弛素D抑制F-肌动蛋白可修复HG对线粒体动力学和功能的损伤作用。相反，F-肌动蛋白聚合诱导剂茉莉酸内酯加重了线粒体分裂和功能障碍。
F-肌动蛋白通过与DRP1相互作用促进HG诱导的线粒体分裂，进而诱导线粒体自噬并损害SMG细胞中的线粒体功能，最终损伤SMG。
