forms lyso-PC and CL, and enriches the specific acyl chain of cardiolipin. The process has been shown to be specific for linoleoyl-containing PC. Such remodeling processes converts cardiolipin into a mature composition that contains a predominance of tetralinoleoyl moieties. CL remodeling in mammals requires additional enzymes, such as monolysocardiolipin acyltransferase (MLCLAT), acyl-CoA:lysocardiolipin acyltransferase (ALCAT), and phospholipase. The process enables the proper function of cardiolipin. Acyl specificity and sensing curvature Tafazzin in CL remodeling has been shown to have a clear preference for linoleoyl-containing PC in forming mature CL. This specificity leads a mature composition of CL that contains a predominance of tetralinoleoyl moieties, which leads to the enrichment of tetralinoleoyl-cardiolipin (CL4). The preference for lineoyl groups has been reported to be ten times greater than that of oleoyl groups and twenty times greater than that of arachidonoyl groups. Conflicting explanations for this preference have included causation from energy minimization with influences by the surrounding microenvironment, known as the thermodynamic remodeling hypothesis, or the inherent enzymatic preference of tafazzin for specific acyl residues. Tafazzin and cardiolipin in mitochondrial structure and function Cardiolipin is a complex glycerophospholipid which contains 4 acyl groups linked to three glycerol moietie localized in the mitochondrial inner membrane. These acyl groups include oleic acid and linoleic acid. Due to this composition, cardiolipin exhibits a conical structure, which allows for membrane curvature called cristae. Further, CL plays important roles in oxidative phosphorylation by stabilizing the chain complexes with its linkages between acyl chains, binding to the c-rings of ATP synthase for proper function, maintaining respiratory chain supercomplex formation with proteins localized in the inner mitochondrial matrix including ATP/ADP translocase, pyruvate carrier, carnitine carrier, and all of the respiratory chain complexes (I, III, IV, V). Cardiolipin also facilitates proton trapping in the intermembrane space to aid ATP synthase in channeling protons into the mitochondrial matrix. Properly formed CL is critical in maintaining mitochondrial shape, energy production, and protein transport within cells, and remodeling by tafazzin aids in removing and replacing acyl chains damaged by oxidative stress. During apoptosis and similar processes, CL is known to act as a platform for proteins and other machinery involved with its interactions with members of the Bcl-2 family, caspases, Bid, Bax, and Bak. Clinical significance Mutations in the TAFAZZIN gene have been associated with a number of mitochondrial deficiencies and associated disorders including Barth syndrome, dilated cardiomyopathy (DCM), hypertrophic DCM, endocardial fibroelastosis, and