title: Cardiolipin asymmetry, oxidation and signaling.
abstract: 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.
authors.affiliation: Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: kagan@pitt.edu.
authors.forename: Valerian E
authors.initials: VE
authors.lastname: Kagan
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15219, USA; Center for Neuroscience, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Charleen T
authors.initials: CT
authors.lastname: Chu
authors.affiliation: Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Yulia Y
authors.initials: YY
authors.lastname: Tyurina
authors.affiliation: Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Amin
authors.initials: A
authors.lastname: Cheikhi
authors.affiliation: Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Hülya
authors.initials: H
authors.lastname: Bayir
mesh_terms: D017209:Apoptosis; D002308:Cardiolipins / Q000737:chemistry* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D063306:Mitophagy; D010084:Oxidation-Reduction; D015398:Signal Transduction
chemical_list: D002308:Cardiolipins
keywords: Apoptosis; Cardiolipin; Cardiolipin asymmetry; Cardiolipin oxidation mitochondria; Mitophagy