N-acylated glycerophospholipids and their derivatives.

Phospholipids (PL) in cerebral cortex from patients with infantile (INCL or CLN1) and juvenile (JNCL or CLN3) forms of neuronal ceroid-lipofuscinosis (NCL) and controls were analysed by normal phase HPLC and on-line electrospray ionization ion-trap mass spectrometric detection (LC-ESI-MS). The method provided quantitative data on numerous molecular species of different PL classes, which are not achieved by using the conventional chromatographic methods. Compared with the controls, the INCL brains contained proportionally more phosphatidylcholine (PC), and less phosphatidylethanolamine (PE) and phosphatidylserine (PS). Different molecular species of PC, PE, PS, phosphatidylinositol and sphingomyelin were quantified using multiple internal PL standards that differed in fatty acyl chain length and thus allowed correction for chain length dependency of instrument response. In INCL cortex, which had lost 65% of the normal PL content, the proportions of polyunsaturated molecular species, especially the PS and PE that contained docosahexaenoic acid (22:6n-3), were dramatically decreased. The membranes may have adapted to this alteration by increasing the proportions of PL molecules substituted with monounsaturated and short-chain fatty acids. Lysobisphosphatidic acid was highly elevated in the INCL brain and consisted mostly of polyunsaturated species. It is possible that changes in the composition of PL membranes accelerate progression of INCL by altering signalling and membrane trafficking in neurons.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1471-4159.2003.01602.x

Analysis of phospholipid molecular species in brains from patients with infantile and juvenile neuronal-ceroid lipofuscinosis using liquid chromatography-electrospray ionization mass spectrometry.

The late endosomes/endo-lysosomes of vertebrates contain an atypical phospholipid, lysobisphosphatidic acid (LBPA) (also termed bis[monoacylglycero]phosphate [BMP]), which is not detected elsewhere in the cell. LBPA is abundant in the membrane system present in the lumen of this compartment, including intralumenal vesicles (ILVs). In this review, the current knowledge on LBPA and LBPA-containing membranes will be summarized, and their role in the control of endosomal cholesterol will be outlined. Some speculations will also be made on how this system may be overwhelmed in the cholesterol storage disorder Niemann-Pick C. Then, the roles of intralumenal membranes in endo-lysosomal dynamics and functions will be discussed in broader terms. Likewise, the mechanisms that drive the biogenesis of intralumenal membranes, including ESCRTs, will also be discussed, as well as their diverse composition and fate, including degradation in lysosomes and secretion as exosomes. This review will also discuss how intralumenal membranes are hijacked by pathogenic agents during intoxication and infection, and what is the biochemical composition and function of the intra-endosomal lumenal milieu. Finally, this review will allude to the size limitations imposed on intralumenal vesicle functions and speculate on the possible role of LBPA as calcium chelator in the acidic calcium stores of endo-lysosomes.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/tra.12715

Life in the lumen: The multivesicular endosome.

Bis(monoacylglycero)phosphate (BMP) is a structural isomer of phosphatidylglycerol that exhibits an unusual sn1:sn1' stereoconfiguration, based on the position of the phosphate moiety on its two glycerol units. Early works have underlined the high concentration of BMP in the lysosomal compartment, especially during some lysosomal storage disorders and drug-induced phospholipidosis. Despite numerous studies, both biosynthetic and degradative pathways of BMP remained not completely elucidated. More recently, BMP has been localized in the internal membranes of late endosomes where it forms specialized lipid domains. Its involvement in both dynamics and lipid/protein sorting functions of late endosomes has started to be documented, especially in the control of cellular cholesterol distribution. BMP also plays an important role in the late endosomal/lysosomal degradative pathway. Another peculiarity of BMP is to be naturally enriched in docosahexaenoic acid and/or to specifically incorporate this fatty acid compared to other polyunsaturated fatty acids, which may confer specific biophysical and functional properties to this phospholipid. This review summarizes and updates our knowledge on BMP with an emphasis on its possible implication in human health and diseases, especially in relation to cholesterol homeostasis.

K Sandelin

Papers

Experimentally caused proliferation of lysosomes in cultured BHK cells involving an increase of biphosphatidic acids and triglycerides.