Phosphatidic Acid and Cardiolipin Coordinate Mitochondrial Dynamics

Shoichiro Kameoka, Yoshihiro Adachi, Koji Okamoto, Miho Iijima, Hiromi Sesaki

Research output: Contribution to journalReview articlepeer-review

Abstract

Membrane organelles comprise both proteins and lipids. Remodeling of these membrane structures is controlled by interactions between specific proteins and lipids. Mitochondrial structure and function depend on regulated fusion and the division of both the outer and inner membranes. Here we discuss recent advances in the regulation of mitochondrial dynamics by two critical phospholipids, phosphatidic acid (PA) and cardiolipin (CL). These two lipids interact with the core components of mitochondrial fusion and division (Opa1, mitofusin, and Drp1) to activate and inhibit these dynamin-related GTPases. Moreover, lipid-modifying enzymes such as phospholipases and lipid phosphatases may organize local lipid composition to spatially and temporarily coordinate a balance between fusion and division to establish mitochondrial morphology. Mitochondrial fusion and division play important roles in mitochondrial size, number, distribution, function, and turnover. Cardiolipin (CL) promotes both mitochondrial division and inner membrane fusion. Phosphatidic acid (PA) inhibits mitochondrial division and stimulates mitochondrial outer membrane fusion. Recent studies have identified phospholipases and lipid phosphatases, such as mitochondria-localized phospholipase D (MitoPLD), PA-preferring phospholipase A1 (PA-PLA1), and lipin 1b, that control the levels of CL and PA in mitochondria. Lipid-modifying enzymes could provide mechanisms that coordinate mitochondrial dynamics.

Original languageEnglish (US)
Pages (from-to)67-76
Number of pages10
JournalTrends in Cell Biology
Volume28
Issue number1
DOIs
StatePublished - Jan 2018

Keywords

  • dynamin-related GTPase
  • lipid phosphatase
  • membrane
  • mitochondrial division
  • mitochondrial fusion
  • phospholipase
  • phospholipids

ASJC Scopus subject areas

  • Cell Biology

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