A brain-enriched drp1 isoform associates with lysosomes, late endosomes, and the plasma membrane

Kie Itoh, Yoshihiro Adachi, Tatsuya Yamada, Takamichi L. Suzuki, Takanobu Otomo, Heidi M. McBride, Tamotsu Yoshimori, Miho Iijima, Hiromi Sesaki

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)11809-11822
Number of pages14
JournalJournal of Biological Chemistry
Volume293
Issue number30
DOIs
StatePublished - Jul 27 2018

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'A brain-enriched drp1 isoform associates with lysosomes, late endosomes, and the plasma membrane'. Together they form a unique fingerprint.

Cite this