title: Homeostasis of phospholipids - The level of phosphatidylethanolamine tightly adapts to changes in ethanolamine plasmalogens.
abstract: Ethanolamine plasmalogens constitute a group of ether glycerophospholipids that, due to their unique biophysical and biochemical properties, are essential components of mammalian cellular membranes. Their importance is emphasized by the consequences of defects in plasmalogen biosynthesis, which in humans cause the fatal disease rhizomelic chondrodysplasia punctata (RCDP). In the present lipidomic study, we used fibroblasts derived from RCDP patients, as well as brain tissue from plasmalogen-deficient mice, to examine the compensatory mechanisms of lipid homeostasis in response to plasmalogen deficiency. Our results show that phosphatidylethanolamine (PE), a diacyl glycerophospholipid, which like ethanolamine plasmalogens carries the head group ethanolamine, is the main player in the adaptation to plasmalogen insufficiency. PE levels were tightly adjusted to the amount of ethanolamine plasmalogens so that their combined levels were kept constant. Similarly, the total amount of polyunsaturated fatty acids (PUFAs) in ethanolamine phospholipids was maintained upon plasmalogen deficiency. However, we found an increased incorporation of arachidonic acid at the expense of docosahexaenoic acid in the PE fraction of plasmalogen-deficient tissues. These data show that under conditions of reduced plasmalogen levels, the amount of total ethanolamine phospholipids is precisely maintained by a rise in PE. At the same time, a shift in the ratio between ω-6 and ω-3 PUFAs occurs, which might have unfavorable, long-term biological consequences. Therefore, our findings are not only of interest for RCDP but may have more widespread implications also for other disease conditions, as for example Alzheimer's disease, that have been associated with a decline in plasmalogens.
authors.affiliation: Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Vienna, Austria. Electronic address: fabian.dorninger@meduniwien.ac.at.
authors.forename: Fabian
authors.initials: F
authors.lastname: Dorninger
authors.affiliation: Heidelberg University Biochemistry Center, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany. Electronic address: broddealexander@johndeere.com.
authors.forename: Alexander
authors.initials: A
authors.lastname: Brodde
authors.affiliation: Department of Human Genetics and Pediatrics, McGill University-Montreal Children's Hospital, 4060 Ste-Catherine West, PT-406.2, Montreal, QC H3Z 2Z3, Canada. Electronic address: nancy.braverman@mcgill.ca.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Braverman
authors.affiliation: Peroxisomal Diseases Laboratory, The Hugo W Moser Research Institute, The Kennedy Krieger Institute, 707 N. Broadway, Baltimore, MD 21205, USA. Electronic address: mosera@kennedykrieger.org.
authors.forename: Ann B
authors.initials: AB
authors.lastname: Moser
authors.affiliation: Heidelberg University Biochemistry Center, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany. Electronic address: wilhelm.just@bzh.uni-heidelberg.de.
authors.forename: Wilhelm W
authors.initials: WW
authors.lastname: Just
authors.affiliation: Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Vienna, Austria. Electronic address: sonja.forss-petter@meduniwien.ac.at.
authors.forename: Sonja
authors.initials: S
authors.lastname: Forss-Petter
authors.affiliation: Heidelberg University Biochemistry Center, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany. Electronic address: britta.bruegger@bzh.uni-heidelberg.de.
authors.forename: Britta
authors.initials: B
authors.lastname: Brügger
authors.affiliation: Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Vienna, Austria. Electronic address: johannes.berger@meduniwien.ac.at.
authors.forename: Johannes
authors.initials: J
authors.lastname: Berger
mesh_terms: D000217:Acyltransferases / Q000172:deficiency* / Q000235:genetics; D000222:Adaptation, Physiological; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D018902:Chondrodysplasia Punctata, Rhizomelic / Q000201:enzymology* / Q000235:genetics; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology*; D020022:Genetic Predisposition to Disease; D066128:Gray Matter / Q000201:enzymology*; D006706:Homeostasis; D006801:Humans; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D010955:Plasmalogens / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D010714:Phosphatidylethanolamines; D010955:Plasmalogens; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; C483858:phosphatidylethanolamine; D000217:Acyltransferases; C020051:glycerone-phosphate O-acyltransferase
keywords: Alzheimer's disease; Arachidonic acid; Compensation; Docosahexaenoic acid; Peroxisome; Plasmalogen