Identification and biophysical characterization of a very-long-chain-fatty-acid-substituted phosphatidylinositol in yeast subcellular membranes
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Morphological analysis of a conditional yeast mutant in acetyl-CoA carboxylase acc1ts/mtr7, the rate-limiting enzyme of fatty acid synthesis, suggested that the synthesis of C26 VLCFAs (very-long-chain fatty acids) is important for maintaining the structure and function of the nuclear membrane. To characterize this C26-dependent pathway in more detail, we have now examined cells that are blocked in pathways that require C26. In yeast, ceramide synthesis and remodelling of GPI (glycosylphosphatidylinositol)-anchors are two pathways that incorporate C26 into lipids. Conditional mutants blocked in either ceramide synthesis or the synthesis of GPI anchors do not display the characteristic alterations of the nuclear envelope observed in acc1ts, indicating that the synthesis of another C26-containing lipid may be affected in acc1ts mutant cells. Lipid analysis of isolated nuclear membranes revealed the presence of a novel C26-substituted PI (phosphatidylinositol). This C26-PI accounts for approx. 1% of all the PI species, and is present in both the nuclear and the plasma membrane. Remarkably, this C26-PI is the only C26-containing glycerophospholipid that is detectable in wild-type yeast, and the C26-substitution is highly specific for the sn-1 position of the glycerol backbone. To characterize the biophysical properties of this lipid, it was chemically synthesized. In contrast to PIs with normal long-chain fatty acids (C16 or C18), the C26-PI greatly reduced the bilayer to hexagonal phase transition of liposomes composed of 1,2-dielaidoyl-sn-glycero-3-phosphoethanolamine (DEPE). The biophysical properties of this lipid are thus consistent with a possible role in stabilizing highly curved membrane domains.
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VLCFAs influence membrane properties such as curvature and permeability.
“VLCFAs are thought to influence membrane properties such as curvature and permeability46,47.”
From Peroxisomal very long-chain fatty acid transport is targeted by herpesviruses and the antiviral host response (2022) · cites this paper as [46]
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Phenotypic Overlap between Atopic Dermatitis and Autism
Shin, K., Crumrine, D. A., Kim, S., Lee, Y., Kim, B., Abuabara, K., Park, C., Uchida, Y., Wakefield, J. S., Meyer, J. M., et al. (2022) · Vide Leaf, Hyderabad eBooks · doi:10.37247/pans2ed.2.22.9
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Additional file 1 of Phenotypic overlap between atopic dermatitis and autism
Shin, K.-O., Crumrine, D. A., Kim, S., Lee, Y., Kim, B., Abuabara, K., Park, C., Uchida, Y., Wakefield, J. S., Meyer, J. M., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14826232
- Authors
- SCHNEITER, R., BRÜGGER, B., AMANN, C. M., PRESTWICH, G. D., EPAND, R. F., ZELLNIG, G., WIELAND, F. T., & EPAND, R. M.
- Affiliations
- University of Fribourg (CH)
- Heidelberg University (DE)
- University of Utah (US)
- McMaster University (CA)
- University of Graz (AT)
- Corresponding author
- SCHNEITER, Roger
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2004-07-27
- Volume
- 381
- Issue
- 3
- Pages
- 941-949
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1133906
- OpenAlex
- W2100088060
- Cited by
- 98
- References
- 47
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 3 · 2014: 5 · 2013: 3 · 2012: 11
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- RERO DOC (Universität Bern) (submittedVersion)
- Funders
- National Science Foundation
- University of Utah
- Deutsche Forschungsgemeinschaft
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (065925)
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS029632)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- very long chain fatty acids, phosphatidylinositol, nuclear envelope, ceramide synthesis, glycosylphosphatidylinositol anchor, lipid bilayer phase transition, membrane curvature, yeast
- MeSH terms
- Acyltransferases, Ceramides, Fatty Acids, Intracellular Membranes, Lipids, Models, Molecular, Nuclear Envelope, Phosphatidylinositols, Saccharomyces cerevisiae, Mass Spectrometry, Glycosylphosphatidylinositols, Serine C-Palmitoyltransferase
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