Drp1 Tubulates the ER in a GTPase-Independent Manner

• Published in: Molecular cell Vol. 80; no. 4; pp. 621 - 632.e6
• Main Authors: Adachi, Yoshihiro, Kato, Takashi, Yamada, Tatsuya, Murata, Daisuke, Arai, Kenta, Stahelin, Robert V., Chan, David C., Iijima, Miho, Sesaki, Hiromi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.11.2020
• Subjects: Animals; Drp1; Dynamins - genetics; Dynamins - metabolism; Dynamins - physiology; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - metabolism; GTP Phosphohydrolases - genetics; GTP Phosphohydrolases - metabolism; Guanosine Triphosphate - metabolism; Humans; Mice; Mice, Knockout; mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; mitochondrial division; Mitochondrial Dynamics; Oligopeptides - pharmacology; organelle contact sites; phosphaditic acid; the endoplasmic reticulum; organelle contact sites; mitochondria; phosphaditic acid; the endoplasmic reticulum; Drp1; mitochondrial division
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2020.10.013

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. [Display omitted] •Drp1 is associated with the ER•Drp1 shapes the ER into tubules independently of oligomerization and GTP hydrolysis•Octadecapeptide554–571 in the variable domain is sufficient for membrane tubulation•ER tubules formed by Drp1 promote mitochondrial division Adachi et al. report that Drp1 shapes the ER into tubules independently of GTP hydrolysis. 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.