title: [Metabolism and biological function of cardiolipin].
abstract: Cardiolipin (CL) is a phospholipid, which is exclusively located in mitochondria, and has a unique structure that consists of 2 phosphate residues and 4 kinds of fatty acyl chains. Cardiolipin plays an important role in regulating various kinds of mitochondrial proteins such as electron transport complexes, carrier proteins and phosphate kinases, and is also essential for the organization of particular mitochondrial structures such as cristae and contact sites. Mitochondrial phospholipase D hydrolyzes CL to produce phosphatidic acid, which is required for mitochondrial fusion. Oxidative stress-induced peroxidation of CL occurs because CL is rich in polyunsaturated fatty acids, especially linoleic acid. Accumulation of CL hydroperoxide (CLOOH) triggers the initiation of apoptosis. Formation of CLOOH causes the release of proapoptotic factors such as cytochrome c from the inner mitochondrial membrane and triggers opening of the permeability transition pore. Levels of CL decrease in the heart following ischemia or disease. Apoptosis is enhanced in temperature-dependent mutant cells whose amounts of CL reduce to half when compared to that of wild type cells. Low levels of CL cause the accumulation of CLOOH and enhance sensitivity to apoptosis. Accumulation of CLOOH in mitochondria causes instability of the membrane, because swelling of mitochondria is induced by the presence of CLOOH in the membrane and is significantly enhanced in CLOOH-loaded mitochondria by the addition of inducer of swelling.
authors: School of Pharmaceutical Sciences, Kitasato University. nakagaway@pharm.kitasato-u.ac.jp
authors: Yasuhito
authors: Y
authors: Nakagawa
mesh_terms: D000818:Animals; D017209:Apoptosis; D002308:Cardiolipins / Q000737:chemistry / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism / Q000502:physiology; D029721:Drosophila Proteins; D006801:Humans; D019787:Linoleic Acid; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000378:metabolism / Q000502:physiology; D008928:Mitochondria / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D010712:Phosphatidic Acids / Q000502:physiology; D010739:Phospholipase D / Q000502:physiology; D044767:Ubiquitin-Protein Ligases
chemical_list: D002308:Cardiolipins; D029721:Drosophila Proteins; D008054:Lipid Peroxides; D024101:Mitochondrial Proteins; D010712:Phosphatidic Acids; D045304:Cytochromes c; D019787:Linoleic Acid; C471151:hyd protein, Drosophila; D044767:Ubiquitin-Protein Ligases; D010739:Phospholipase D