Cardiolipin fingerprinting of leukocytes by MALDI-TOF/MS as a screening tool for Barth syndrome

Abstract

mitochondrial respiratory chain dysfunction ( 1-4 ). It results from loss-of-function mutations of the tafazzin ( TAZ ) gene ( 5 ).The major consequence of this loss-of-function is the defi cient remodeling of the mitochondrial phospholipid cardiolipin (CL), a process that normally leads to the mature acyl composition ( 6, 7 ). CL is the signature lipid of mitochondria, where it is an important constituent of the inner membrane, essential for supercomplex formation, oxidative phosphorylation (i.e., mitochondrial energy metabolism), and protein import, and is capable of triggering mitophagy and mitochondria-mediated apoptosis (8)(9)(10)(11)(12)(13)(14)(15)(16). Because the remodeling of CL is deficient in BTHS, biochemical abnormalities in patients include a decreased level of mature CL (CLm), an increased level of monolysocardiolipin (MLCL), and altered CL acyl composition [i.e., the presence of immature CL (CLi) species].Historically, the diagnosis of BTHS has relied on identifi cation of the clinical symptoms accompanied by neutropenia and 3-MGCA and has then been confi rmed by the fi nding of TAZ mutations. More recently, assays of CL alone or of the ratio of CL to MLCL have been used in Europe. However, each of these diagnostic approaches has problems. There are multiple reports of false-negative disease detection by urinary organic acid screening ( 4 ). TAZ sequencing is relatively slow and expensive, and CL analysis involves many steps including extraction of lipids and isolation of CL molecular species by complex chromatographic techniques. Consequently, although measurement of CL/MLCL ratio has 100% diagnostic sensitivity and specifi city, it is only available in a few clinical laboratories

<p>Genetic ablation of TAZ induces HepG2 liver cancer cell apoptosis through activating the CaMKII/MIEF1 signaling pathway</p>

“…In fatty liver disease, TAZ downregulation promotes lipid accumulation and suppresses mitochondrial respiratory function 57. Moreover, TAZ is also involved in mitophagy regulation,58 mitochondrial cardiolipin metabolism,59 and the mitochondrial redox balance 60. In the present study, we found that TAZ deletion evoked mitochondrial bioenergetics disorder, mitochondrial oxidative injury, mitochondrial potential reduction, mitochondrial fission, and mitochondrial apoptosis.…”

Lipid profiling of parkin‐mutant human skin fibroblasts

“…Recently MALDI‐TOF/MS analysis has been successfully used to directly acquire lipid profiles of biological samples (Angelini, Babudri, Lobasso, & Corcelli, ; Angelini et al, , ; Angelini, Vortmeier, Corcelli, & Fuchs, ; Vitale et al, ). One of the advantages of this analytical approach is that minute amounts of cell membranes are required for lipid analyses.…”

Lipid Profile Changes During the Development of Artemia franciscana, From Cysts to the First Two Naupliar Stages

“…Three microliter of lipid samples in chloroform solution were diluted in 27 μl of 2-propanol/acetonitrile (60/40, by volume), then 10 μl of the diluted solution were mixed with 10 μl of matrix solution (9-AA, 10 mg/ml in 2-propanol/acetonitrile 60/40, by volume), as previously described (Sun et al, 2008; Angelini et al, 2015). At variance, spectra of neutral lipids were acquired by preparing the same matrix solution in the presence of sodium acetate, as previously described (Sun et al, 2008).…”