Known unknowns of cardiolipin signaling: The best is yet to come

John J. Maguire, Yulia Y. Tyurina, Dariush Mohammadyani, Aleksandr A. Kapralov, Tamil S. Anthonymuthu, Feng Qu, Andrew A. Amoscato, Louis J. Sparvero, Vladimir A. Tyurin, Joan Planas-Iglesias, Rong Rong He, Judith Klein-Seetharaman, Hülya Bayır, Valerian E. Kagan

Research output: Contribution to journalArticlepeer-review

97 Scopus citations


Since its discovery 75 years ago, a wealth of knowledge has accumulated on the role of cardiolipin, the hallmark phospholipid of mitochondria, in bioenergetics and particularly on the structural organization of the inner mitochondrial membrane. A surge of interest in this anionic doubly-charged tetra-acylated lipid found in both prokaryotes and mitochondria has emerged based on its newly discovered signaling functions. Cardiolipin displays organ, tissue, cellular and transmembrane distribution asymmetries. A collapse of the membrane asymmetry represents a pro-mitophageal mechanism whereby externalized cardiolipin acts as an “eat-me” signal. Oxidation of cardiolipin's polyunsaturated acyl chains - catalyzed by cardiolipin complexes with cytochrome c. - is a pro-apoptotic signal. The messaging functions of myriads of cardiolipin species and their oxidation products are now being recognized as important intracellular and extracellular signals for innate and adaptive immune systems. This newly developing field of research exploring cardiolipin signaling is the main subject of this review. This article is part of a Special Issue entitled: Lipids of Mitochondria edited by Guenther Daum.

Original languageEnglish (US)
Pages (from-to)8-24
Number of pages17
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Issue number1
StatePublished - Jan 1 2017
Externally publishedYes


  • Apoptosis
  • Cardiolipin oxidation
  • Cardiolipin signaling
  • Innate and adaptive immunity
  • Mitophagy
  • Peroxidase

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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