Drp1 polymerization stabilizes curved tubular membranes similar to those of constricted mitochondria

J Cell Sci. 2018 Apr 19;132(4):jcs208603. doi: 10.1242/jcs.208603.

Abstract

Dynamin-related protein 1 (Drp1), an 80 kDa mechanochemical GTPase of the dynamin superfamily, is required for mitochondrial division in mammals. Despite the role of Drp1 dysfunction in human disease, its molecular mechanism remains poorly understood. Here, we examined the effect of Drp1 on membrane curvature using tubes pulled from giant unilamellar vesicles (GUVs). We found that GTP promoted rapid rearrangement of Drp1 from a uniform distribution to discrete foci, in line with the assembly of Drp1 scaffolds at multiple nucleation sites around the lipid tube. Polymerized Drp1 preserved the membrane tube below the protein coat, also in the absence of pulling forces, but did not induce spontaneous membrane fission. Strikingly, Drp1 polymers stabilized membrane curvatures similar to those of constricted mitochondria against pressure changes. Our findings support a new model for mitochondrial division whereby Drp1 mainly acts as a scaffold for membrane curvature stabilization, which sets it apart from other dynamin homologs.

Keywords: Curvature stabilizer; Dynamin-related protein 1; Membrane biophysics; Membrane curvature; Mitochondrial fission; Protein self-assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiolipins / metabolism
  • Cytokinesis / physiology
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • Guanosine Triphosphate / metabolism
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Mitochondria / metabolism*
  • Mitochondrial Dynamics / physiology*
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Polymerization
  • Protein Multimerization / physiology

Substances

  • Cardiolipins
  • Microtubule-Associated Proteins
  • Mitochondrial Proteins
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • DNM1L protein, human