Coincident Phosphatidic Acid Interaction Restrains Drp1 in Mitochondrial Division

Yoshihiro Adachi, Kie Itoh, Tatsuya Yamada, Kara L. Cerveny, Takamichi L. Suzuki, Patrick Macdonald, Michael A. Frohman, Rajesh Ramachandran, Miho Iijima, Hiromi Sesaki

Research output: Contribution to journalArticlepeer-review

Abstract

Mitochondria divide to control their size, distribution, turnover, and function. Dynamin-related protein 1 (Drp1) is a critical mechanochemical GTPase that drives constriction during mitochondrial division. It is generally believed that mitochondrial division is regulated during recruitment of Drp1 to mitochondria and its oligomerization into a division apparatus. Here, we report an unforeseen mechanism that regulates mitochondrial division by coincident interactions of Drp1 with the head group and acyl chains of phospholipids. Drp1 recognizes the head group of phosphatidic acid (PA) and two saturated acyl chains of another phospholipid by penetrating into the hydrophobic core of the membrane. The dual phospholipid interactions restrain Drp1 via inhibition of oligomerization-stimulated GTP hydrolysis that promotes membrane constriction. Moreover, a PA-producing phospholipase, MitoPLD, binds Drp1, creating a PA-rich microenvironment in the vicinity of a division apparatus. Thus, PA controls the activation of Drp1 after the formation of the division apparatus.

Original languageEnglish (US)
Pages (from-to)1034-1043
Number of pages10
JournalMolecular cell
Volume63
Issue number6
DOIs
StatePublished - Sep 15 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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