Drp1 Tubulates the ER in a GTPase-Independent Manner

Adachi, Y.; Kato, T.; Yamada, T.; Murata, D.; Arai, K.; Stahelin, R. V.; Chan, D. C.; Iijima, M.; Sesaki, H., Drp1 Tubulates the ER in a GTPase-Independent Manner. Mol Cell 2020, 80 (4), 621-632.e6.

Interaction Type: Protein-small molecule

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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