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A loss of CL content, alterations in its acyl chain composition, and\/or CL peroxidation have been associated with mitochondrial dysfunction in multiple tissues in a variety of pathological conditions, including ischemia, hypothyroidism, aging, and heart failure. Recently, aberrations in CL metabolism have been implicated as a primary causative factor in the cardioskeletal myopathy known as Barth syndrome, underscoring an important role of CL in human health and disease. The purpose of this review is to provide an overview of evidence that has linked changes in the CL profile to mitochondrial dysfunction in various pathological conditions. In addition, a brief overview of CL function and biosynthesis, and a discussion of methods used to examine CL in biological tissues are provided.<\/jats:p>","DOI":"10.1152\/ajpcell.00243.2006","type":"journal-article","created":{"date-parts":[[2006,8,10]],"date-time":"2006-08-10T00:48:06Z","timestamp":1155170886000},"page":"C33-C44","source":"Crossref","is-referenced-by-count":585,"title":["Role of cardiolipin alterations in mitochondrial dysfunction and disease"],"prefix":"10.1152","volume":"292","author":[{"given":"Adam J.","family":"Chicco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevieve C.","family":"Sparagna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Adibhatla RM, Hatcher JF, Dempsey RJ.Phospholipase A2, hydroxyl radicals, and lipid peroxidation in transient cerebral ischemia.Antioxid Redox Signal5: 647\u2013654, 2003.","DOI":"10.1089\/152308603770310329"},{"key":"R2","doi-asserted-by":"crossref","unstructured":"Adosraku RK, Smith JD, Nicolaou A, Gibbons WA.Tetrahymena thermophila: analysis of phospholipids and phosphonolipids by high-field1H-NMR.Biochim Biophys Acta1299: 167\u2013174, 1996.","DOI":"10.1016\/0005-2760(95)00181-6"},{"key":"R3","doi-asserted-by":"crossref","unstructured":"Ames BN, Liu J.Delaying the mitochondrial decay of aging with acetylcarnitine.Ann NY Acad Sci1033: 108\u2013116, 2004.","DOI":"10.1196\/annals.1320.010"},{"key":"R4","doi-asserted-by":"crossref","unstructured":"Ames BN, Shigenaga MK, Hagen TM.Mitochondrial decay in aging.Biochim Biophys Acta1271: 165\u2013170, 1995.","DOI":"10.1016\/0925-4439(95)00024-X"},{"key":"R5","doi-asserted-by":"crossref","unstructured":"Barth PG, Valianpour F, Bowen VM, Lam J, Duran M, Vaz FM, Wanders RJ.X-linked cardioskeletal myopathy and neutropenia (Barth syndrome): an update.Am J Med Genet126: 349\u2013354, 2004.","DOI":"10.1002\/ajmg.a.20660"},{"key":"R6","doi-asserted-by":"crossref","unstructured":"Barth PG, Van den Bogert C, Bolhuis PA, Scholte HR, van Gennip AH, Schutgens RB, Ketel AG.X-linked cardioskeletal myopathy and neutropenia (Barth syndrome): respiratory-chain abnormalities in cultured fibroblasts.J Inherit Metab Dis19: 157\u2013160, 1996.","DOI":"10.1007\/BF01799418"},{"key":"R7","doi-asserted-by":"crossref","unstructured":"Barth PG, Wanders RJ, Vreken P.X-linked cardioskeletal myopathy and neutropenia (Barth syndrome)-MIM 302060.J Pediatr135: 273\u2013276, 1999.","DOI":"10.1016\/S0022-3476(99)70118-6"},{"key":"R8","doi-asserted-by":"crossref","unstructured":"Beal MF.Mitochondria, oxidative damage, and inflammation in Parkinson's disease.Ann NY Acad Sci991: 120\u2013131, 2003.","DOI":"10.1111\/j.1749-6632.2003.tb07470.x"},{"key":"R9","doi-asserted-by":"crossref","unstructured":"Beleznai Z, Jancsik V.Role of cardiolipin in the functioning of mitochondriall-glycerol-3-phosphate dehydrogenase.Biochem Biophys Res Commun159: 132\u2013139, 1989.","DOI":"10.1016\/0006-291X(89)92414-5"},{"key":"R10","doi-asserted-by":"crossref","unstructured":"Berger A, German JB, Gershwin ME.Biochemistry of cardiolipin: sensitivity to dietary fatty acids.Adv Food Nutr Res37: 259\u2013338, 1993.","DOI":"10.1016\/S1043-4526(08)60118-7"},{"key":"R11","doi-asserted-by":"crossref","unstructured":"Beyer K, Nuscher B.Specific cardiolipin binding interferes with labeling of sulfhydryl residues in the adenosine diphosphate\/adenosine triphosphate carrier protein from beef heart mitochondria.Biochemistry35: 15784\u201315790, 1996.","DOI":"10.1021\/bi9610055"},{"key":"R12","doi-asserted-by":"crossref","unstructured":"Bione S, D'Adamo P, Maestrini E, Gedeon AK, Bolhuis PA, Toniolo D.A novel X-linked gene, G4.5 is responsible for Barth syndrome.Nat Genet12: 385\u2013389, 1996.","DOI":"10.1038\/ng0496-385"},{"key":"R13","doi-asserted-by":"crossref","unstructured":"Brandner K, Mick DU, Frazier AE, Taylor RD, Meisinger C, Rehling P.Taz1, an outer mitochondrial membrane protein, affects stability and assembly of inner membrane protein complexes: implications for Barth syndrome.Mol Biol Cell16: 5202\u20135214, 2005.","DOI":"10.1091\/mbc.e05-03-0256"},{"key":"R14","doi-asserted-by":"crossref","unstructured":"Brandt MA, Powers-Lee SG.The interaction of cardiolipin with rat liver carbamoyl phosphate synthetase I.Arch Biochem Biophys290: 14\u201320, 1991.","DOI":"10.1016\/0003-9861(91)90585-7"},{"key":"R15","doi-asserted-by":"crossref","unstructured":"Buckland AG, Kinkaid AR, Wilton DC.Cardiolipin hydrolysis by human phospholipases A2. 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