Drp1 Tubulates the ER in a GTPase-Independent Manner

• DOI: 10.1016/j.molcel.2020.10.013
• Publication Date: 2020-11-05T03:05:26Z
• Authors: Yoshihiro Adachi; Takashi Kato; Tatsuya Yamada; Daisuke Murata; Kenta Arai; Robert V. Stahelin; David C. Chan; Miho Iijima; Hiromi Sesaki
• Keywords: Organelle

Mitochondria are highly dynamic organelles that continuously grow, divide, and fuse. The division of mitochondria is crucial for human health. During mitochondrial division, the mechano-guanosine triphosphatase (GTPase) dynamin-related protein (Drp1) severs mitochondria at endoplasmic reticulum (ER)-mitochondria contact sites, where peripheral ER tubules interact with mitochondria. Here, we report that Drp1 directly shapes peripheral ER tubules in human and mouse cells. This ER-shaping activity is independent of GTP hydrolysis and located in a highly conserved peptide of 18 amino acids (termed D-octadecapeptide), which is predicted to form an amphipathic α helix. Synthetic D-octadecapeptide tubulates liposomes in vitro and the ER in cells. ER tubules formed by Drp1 promote mitochondrial division by facilitating ER-mitochondria interactions. Thus, Drp1 functions as a two-in-one protein during mitochondrial division, with ER tubulation and mechano-GTPase activities.