|Dynamin-related protein 1 is implicated in endoplasmic reticulum stress-induced pancreatic β-cell apoptosis|
Authors: Liang Peng, Xiuli Men, Wenjian Zhang, Haiyan Wang, Shiqing Xu, Mei Xu, Yaping Xu, Wenying Yang, Jinning Lou
Affiliations: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, P.R. China, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, P.R. China
Published online on: Thursday, April 28, 2011
Pancreatic β-cell dysfunction is a critical component in the pathogenesis of diabetes. Endoplasmic reticulum (ER) stress is one of the factors that induces pancreatic β-cell dysfunction, but the underlying mechanisms have not been well elucidated. In this study, we report that a mitochondrial fission modulator, dynamin-related protein 1 (DRP-1), plays an important role in ER stress-induced β-cell apoptosis. Induction of DRP-1 expression significantly promoted ER stress-induced apoptosis in the DRP-1 WT (DRP-1 wild- type) inducible β-cell line, but not in the DRP-1 K38A (a dominant negative mutant of DRP-1) inducible β-cell line. We further demonstrated that the mitochondrial membrane potential decreased, and that cytochrome c release, caspase-3 activation and generation of reactive oxygen species (ROS) were enhanced by induction of DRP-1 WT, but prevented by DRP-1 K38A in pancreatic β-cells under ER stress conditions. These results indicate that DRP-1 mediates ER stress-induced pancreatic β-cell apoptosis.