Unequivocal Mapping of Molecular Ether Lipid Species by LC–MS/MS in Plasmalogen-Deficient Mice

Abstract

Deficient ether lipid biosynthesis in rhizomelic chondrodysplasia punctata and other disorders is associated with a wide range of severe symptoms including small stature with proximal shortening of the limbs, contractures, facial dysmorphism, congenital cataracts, ichthyosis, spasticity, microcephaly, and mental disability. Mouse models are available but show less severe symptoms. In both humans and mice, it has remained elusive which of the symptoms can be attributed to lack of plasmanyl or plasmenyl ether lipids. The latter compounds, better known as plasmalogens, harbor a vinyl ether double bond conferring special chemical and physical properties. Discrimination between plasmanyl and plasmenyl ether lipids is a major analytical challenge, especially in complex lipid extracts with many isobaric species. Consequently, these lipids are often neglected also in recent lipidomic studies. Here, we present a comprehensive LC–MS/MS based approach that allows unequivocal distinction of these two lipid subclasses based on their chromatographic properties. The method was validated using a novel plasmalogen-deficient mouse model, which lacks plasmanylethanolamine desaturase and therefore cannot form plasmenyl ether lipids. We demonstrate that plasmanylethanolamine desaturase deficiency causes an accumulation of plasmanyl species, a too little studied but biologically important substance class.

Fatty acyl availability modulates cardiolipin composition and alters mitochondrial function in HeLa cells

“…The acyl side-chain composition of CL is highly diverse not only in different organisms but also within tissues of the same organism ( 8 , 9 , 30 ). The postbiosynthetic enzymatic remodeling process of CL plays an important physiological role for mitochondrial membrane constitution, which can cause severe mitochondrial dysfunction, for example, when impaired as in the case of Barth syndrome ( 41 ).…”

“…Prediction of CL profile with modeled FA and CL fragments was used as quality control. Phospholipids were measured as described ( 30 ).…”

Plasmalogens and Chronic Inflammatory Diseases

“…They are found in a variety of organs, cells, and other lipid-rich structures such as the myelin sheath and lipoproteins ( Table 1 ). The highest amount of plasmalogen is found in the brain, while the liver has the lowest amount of plasmalogens ( Koch et al, 2020 ). Choline plasmalogens (also called plasmenylcholine, PC-Pls) are highly enriched in the heart and smooth muscle, while all other organs are enriched with ethanolamine plasmalogens (also called plasmenylethanolamine, PE-Pls).…”

The Emerging Physiological Role of AGMO 10 Years after Its Gene Identification

“…Different analytical strategies have been developed to properly discriminate different ether lipid subclasses, including the generation of structurally informative lithium-salt adducts [ 37 ] and the implementation of instrumentally more demanding MS 3 and MS 4 -fragmentation experiments [ 38 ]. Recently, it has been systematically demonstrated that the chromatographic properties of plasmanyl and plasmenyl lipids are different enough to facilitate their univocal mapping in LC-MS/MS lipidomic experiments [ 39 ].…”