Mitochondrial Remodeling in Endothelial Cells under Cyclic Stretch is Independent of Drp1 Activation

• 作者: Akira Tsukamoto Aya Shinmura Megumi Baba Shigeru Tada Taku Amo
• 来源期刊: 分子与细胞生物力学(英文)
• 学科: 医学
• 关键词: ENDOTHELIAL cells cyclic STRETCH MITOCHONDRIA morphology Drp1.
• 年，卷（期）: 2019,（1）
• 页码范围: 1-12
• 页数: 12页
• 分类号: R73

摘要

Mitochondria in endothelial cells remodel morphologically when supraphysiological cyclic stretch is exerted on the cells.During remodeling,mitochondria become shorter,but how they do so remains elusive.Drp1 is a regulator of mitochondrial morphologies.It shortens mitochondria by shifting the balance from mitochondrial fusion to fission.In this study,we hypothesized that Drp1 activation is involved in mitochondrial remodeling under supraphysiological cyclic stretch.To verify the involvement of Drp1,its activation was first quantified with Western blotting,but Drp1 was not significantly activated in endothelial cells under supraphysiological cyclic stretch.Next,Drp1 activation was inhibited with Mdivi-1,but this did not inhibit mitochondrial remodeling.Intracellular Ca^2+ increase activates Drp1 through calcineurin.First,we inhibited the intracellular Ca^2+ increase with Gd^3+ and thapsigargin,but this did not inhibit mitochondrial remodeling.Next,we inhibited calcineurin with cyclosporin A,but this also did not inhibit mitochondrial remodeling.These results indicate that mitochondrial remodeling under supraphysiological cyclic stretch is independent of Drp1 activation.In endothelial cells under supraphysiological cyclic stretch,reactive oxygen species(ROS)are generated.Mitochondrial morphologies are remodeled by ROS generation.When ROS was eliminated with N-acetyl-L-cysteine,mitochondrial remodeling was inhibited.Furthermore,when the polymerization of the actin cytoskeleton was inhibited with cytochalasin D,mitochondrial remodeling was also inhibited.These results suggest that ROS and actin cytoskeleton are rather involved in mitochondrial remodeling.In conclusion,the present results suggest that mitochondrial remodeling in endothelial cells under supraphysiological cyclic stretch is induced by ROS in association with actin cytoskeleton rather than through Drp1 activation.