F‐actin/DRP1 axis‐mediated mitochondrial fission promotes mitophagy in diabetic submandibular glands

Abstract Background 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. Materials and Methods A diabetic mouse model and a high glucose (HG)‐induced diabetic submandibular gland (SMG) cell model were employed. Results 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. Conclusions 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.