Drp1 Tubulates the ER in a GTPase-Independent Manner

Mol Cell. 2020 Nov 19;80(4):621-632.e6. doi: 10.1016/j.molcel.2020.10.013. Epub 2020 Nov 4.

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.

Keywords: Drp1; mitochondria; mitochondrial division; organelle contact sites; phosphaditic acid; the endoplasmic reticulum.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • 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 / drug effects
  • Mitochondria / metabolism*
  • Mitochondrial Dynamics
  • Oligopeptides / pharmacology

Substances

  • Oligopeptides
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • DNM1L protein, human
  • Dnm1l protein, mouse
  • Dynamins