2026-05-17T05:52:36Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/172102024-09-21T12:11:57Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Kim, Young-Mee author Youn, Seock-Won author Sudhahar, Varadarajan author Das, Archita author Chandhri, Reyhaan author Cuervo Grajal, Henar author Kweon, Junghun author Leanhart, Silvia author He, Lianying author Toth, Peter T author Kitajewski, Jan author Rehman, Jalees author Yoon, Yisang author Cho, Jaehyung author Fukai, Tohru author Ushio-Fukai, Masuko author 2018-06-19 Mitochondrial dynamics are tightly controlled by fusion and fission, and their dysregulation and excess reactive oxygen species (ROS) contribute to endothelial cell (EC) dysfunction. How redox signals regulate coupling between mitochondrial dynamics and endothelial (dys)function remains unknown. Here, we identify protein disulfide isomerase A1 (PDIA1) as a thiol reductase for the mitochondrial fission protein Drp1. A biotin-labeled Cys-OH trapping probe and rescue experiments reveal that PDIA1 depletion in ECs induces sulfenylation of Drp1 at Cys644, promoting mitochondrial fragmentation and ROS elevation without inducing ER stress, which drives EC senescence. Mechanistically, PDIA1 associates with Drp1 to reduce its redox status and activity. Defective wound healing and angiogenesis in diabetic or PDIA1+/- mice are restored by EC-targeted PDIA1 or the Cys oxidation-defective mutant Drp1. Thus, this study uncovers a molecular link between PDIA1 and Drp1 oxidoreduction, which maintains normal mitochondrial dynamics and limits endothelial senescence with potential translational implications for vascular diseases associated with diabetes or aging. Cell Rep. 2018 Jun 19;23(12):3565-3578. 10.1016/j.celrep.2018.05.054 2211-1247 Cell reports 29924999 http://hdl.handle.net/20.500.12105/17210 Redox Regulation of Mitochondrial Fission Protein Drp1 by Protein Disulfide Isomerase Limits Endothelial Senescence.