A brain-enriched Drp1 isoform associates with lysosomes, late endosomes, and the plasma membrane

J Biol Chem. 2018 Jul 27;293(30):11809-11822. doi: 10.1074/jbc.RA117.001253. Epub 2018 May 31.


Dynamin-related protein 1 (Drp1) constricts mitochondria as a mechanochemical GTPase during mitochondrial division. The Drp1 gene contains several alternative exons and produces multiple isoforms through RNA splicing. Here we performed a systematic analysis of Drp1 transcripts in different mouse tissues and identified a previously uncharacterized isoform that is highly enriched in the brain. This Drp1 isoform is termed Drp1ABCD because it contains four alterative exons: A, B, C, and D. Remarkably, Drp1ABCD is located at lysosomes, late endosomes, and the plasma membrane in addition to mitochondria. Furthermore, Drp1ABCD is concentrated at the interorganelle interface between mitochondria and lysosomes/late endosomes. The localizations of Drp1ABCD at lysosomes, late endosomes, and the plasma membrane require two exons, A and B, that are present in the GTPase domain. Drp1ABCD assembles onto these membranes in a manner that is regulated by its oligomerization and GTP hydrolysis. Experiments using lysosomal inhibitors show that the association of Drp1ABCD with lysosomes/late endosomes depends on lysosomal pH but not their protease activities. Thus, Drp1 may connect mitochondria to endosomal-lysosomal pathways in addition to mitochondrial division.

Keywords: GTPase; brain; lysosome; mitochondria; subcellular organelle.

Publication types

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

MeSH terms

  • Animals
  • Brain / metabolism*
  • Cell Membrane / metabolism*
  • Dynamins / analysis
  • Dynamins / metabolism*
  • Endosomes / metabolism*
  • Lysosomes / metabolism*
  • Mice
  • Mitochondria / metabolism
  • Peroxisomes / metabolism
  • Protein Isoforms / analysis
  • Protein Isoforms / metabolism


  • Protein Isoforms
  • Dnm1l protein, mouse
  • Dynamins