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Cardiolipin asymmetry, oxidation and signaling
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  • Description:
    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.

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  • Funding:
    AG026389/AG/NIA NIH HHS/United States
    ES020693/ES/NIEHS NIH HHS/United States
    ES021068/ES/NIEHS NIH HHS/United States
    NS061817/NS/NINDS NIH HHS/United States
    NS065789/NS/NINDS NIH HHS/United States
    NS076511/NS/NINDS NIH HHS/United States
    OH008282/OH/NIOSH CDC HHS/United States
    R01 AG026389/AG/NIA NIH HHS/United States
    R01 ES020693/ES/NIEHS NIH HHS/United States
    R01 HL070755/HL/NHLBI NIH HHS/United States
    R01 HL094488/HL/NHLBI NIH HHS/United States
    R01 NS061817/NS/NINDS NIH HHS/United States
    R01 NS065789/NS/NINDS NIH HHS/United States
    R01 NS076511/NS/NINDS NIH HHS/United States
    U19 AI068021/AI/NIAID NIH HHS/United States
    U19 AI068021/AI/NIAID NIH HHS/United States
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