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Cardiolipin asymmetry, oxidation and signaling.

Kagan-VE; Chu-CT; Tyurina-YY; Cheikhi-A; Bayir-H

Chem Phys Lipids 2014 Apr; 179:64-69

http://dx.doi.org/10.1016/j.chemphyslip.2013.11.010

20045289

Cardiolipins (CLs) are ancient and unusual dimeric phospholipids localized in the plasma membrane of bacteria and in the inner mitochondrial membrane of eukaryotes. In mitochondria, two types of asymmetries--trans-membrane and molecular--are essential determinants of CL functions. In this review, we describe CL-based signaling mitochondrial pathways realized via modulation of trans-membrane asymmetry and leading to externalization and peroxidation of CLs in mitophagy and apoptosis, respectively. We discuss possible mechanisms of CL translocations from the inner leaflet of the inner to the outer leaflet of the outer mitochondrial membranes. We present redox reaction mechanisms of cytochrome c-catalyzed CL peroxidation as a required stage in the execution of apoptosis. We also emphasize the significance of CL-related metabolic pathways as new targets for drug discovery. Finally, a remarkable diversity of polyunsaturated CL species and their oxidation products have evolved in eukaryotes vs. prokaryotes. This diversity--associated with CL molecular asymmetry--is presented as the basis for mitochondrial communications language.

Molecular-structure; Phospholipids; Mammalian-cells; Oxidation; Biological-function; Bacteria; Plasma-membrane; Author Keywords: Cardiolipin; Cardiolipin asymmetry; Cardiolipin oxidation mitochondria; Mitophagy; Apoptosis

Valerian E. Kagan, Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Bridgeside Point, 100 Technology Drive, Suite 350, Pittsburgh, PA 15219

CPLIA4

20140401

Journal Article

kagan@pitt.edu

Grant

2014

Grant-Number-R01-OH-008282; M102014

0009-3084

Manufacturing

Chemistry and Physics of Lipids

PA

University of Pittsburgh at Pittsburgh