Adachi, Yoshihiro and Kato, Takashi and Yamada, Tatsuya and Murata, Daisuke and Arai, Kenta and Stahelin, Robert V. and Chan, David C. and Iijima, Miho and Sesaki, Hiromi (2020) Drp1 Tubulates the ER in a GTPase-Independent Manner. Molecular Cell, 80 (4). pp. 621-632. ISSN 1097-2765. PMCID PMC7680448. doi:10.1016/j.molcel.2020.10.013. https://resolver.caltech.edu/CaltechAUTHORS:20201105-160425351
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Abstract
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.
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| Additional Information: | © 2020 Elsevier. Received 28 April 2020, Revised 10 September 2020, Accepted 9 October 2020, Available online 4 November 2020. We thank past and present members of the Iijima and Sesaki labs for helpful discussions and technical assistance. We are grateful to Dr. H. Otera for providing Drp1-KO and Mff/Fis1 double-KO Hela cells and Dr. A. van der Bliek for anti-Mff antibodies. This work was supported by NIH grants to M.I. (GM131768) and H.S. (GM123266 and GM130695), a grant from Diana Helis Henry Medical Research Foundation and Adrienne Helis Malvin Medical Research Foundation to H.S., and a grant from Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation to H.S. Author Contributions. Y.A., M.I., and H.S. conceived the project. Y.A., T.K., T.Y., D.M., and M.I. performed the experiments. Y.A., K.A., R.V.S., M.I., and H.S. analyzed the data. D.C.C. provided critical reagents. Y.A., T.K., T.Y., K.A., D.M., R.V.S., D.C.C., M.I., and H.S. contributed to discussions. Y.A., M.I., and H.S. wrote the manuscript. The authors declare no competing interests. | ||||||||||||||
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| Subject Keywords: | mitochondria; the endoplasmic reticulum; Drp1; organelle contact sites; phosphaditic acid; mitochondrial division | ||||||||||||||
| Issue or Number: | 4 | ||||||||||||||
| PubMed Central ID: | PMC7680448 | ||||||||||||||
| DOI: | 10.1016/j.molcel.2020.10.013 | ||||||||||||||
| Record Number: | CaltechAUTHORS:20201105-160425351 | ||||||||||||||
| Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20201105-160425351 | ||||||||||||||
| Official Citation: | Yoshihiro Adachi, Takashi Kato, Tatsuya Yamada, Daisuke Murata, Kenta Arai, Robert V. Stahelin, David C. Chan, Miho Iijima, Hiromi Sesaki, Drp1 Tubulates the ER in a GTPase-Independent Manner, Molecular Cell, Volume 80, Issue 4, 2020, Pages 621-632.e6, ISSN 1097-2765, https://doi.org/10.1016/j.molcel.2020.10.013. | ||||||||||||||
| Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||||
| ID Code: | 106463 | ||||||||||||||
| Collection: | CaltechAUTHORS | ||||||||||||||
| Deposited By: | George Porter | ||||||||||||||
| Deposited On: | 06 Nov 2020 15:07 | ||||||||||||||
| Last Modified: | 11 Feb 2022 22:21 |
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