Lipidomics of mitochondria isolated from human fibroblasts

Mitochondrial trifunctional protein (TFP) has a monolysocardiolipin-acyltransferase (MLCL-AT) activity and therefore establishes a link between fatty acid oxidation and cardiolipin remodelling. We hypothesized that TFP deficiency produced changes in cardiolipin and other phospholipid content and composition in mitochondria of TFP cultured fibroblasts. The data showed that phospholipid profiles varied among patient fibroblasts. There was a correlation between genotype and the phospholipid profiles. Two profiles were found when cardiolipin, monolysocardiolipin, and oxidized cardiolipin and other phospholipids were considered, one of them similar to Barth syndrome. We concluded that cardiolipin remodeling may play a role in the pathogenesis of at least some patients with TFP/LCHAD deficiency. A previously described protocol was employed for the identification and quantification of mitochondrial phospholipids (including CL) and oxidized phospholipids by LC-MS/MS [1]. Briefly, lipids were extracted using the Folch method, total phosphate content was quantified, and samples were then analyzed using a LC-MS/MS system. The identification and quantification of the lipid species were achieved with an optimized workflow using SIEVE 2.2 software, and an in-house database. [1]. Chao H, Anthonymuthu TS, Kenny EM, Amoscato AA, Cole LK, Hatch GM et al. Disentangling oxidation/hydrolysis reactions of brain mitochondrial cardiolipins in pathogenesis of traumatic injury. JCI Insight 2018;3(21).