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SHR Neuro Cancer Cardio Lipid Metab Microb

Wolinski, H; Hofbauer, HF; Hellauer, K; Cristobal-Sarramian, A; Kolb, D; Radulovic, M; Knittelfelder, OL; Rechberger, GN; Kohlwein, SD.
Seipin is involved in the regulation of phosphatidic acid metabolism at a subdomain of the nuclear envelope in yeast.
Biochim Biophys Acta. 2015; 1851(11):1450-1464 Doi: 10.1016/j.bbalip.2015.08.003 [OPEN ACCESS]
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Co-authors Med Uni Graz: Kolb Dagmar
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Abstract:: Yeast Fld1 and Ldb16 resemble mammalian seipin, implicated in neutral lipid storage. Both proteins form a complex at the endoplasmic reticulum-lipid droplet (LD) interface. Malfunction of this complex either leads to LD clustering or to the generation of supersized LD (SLD) in close vicinity to the nuclear envelope, in response to altered phospholipid (PL) composition. We show that similar to mutants lacking Fld1, deletion of LDB16 leads to abnormal proliferation of a subdomain of the nuclear envelope, which is tightly associated with clustered LD. The human lipin-1 ortholog, the PAH1 encoded phosphatidic acid (PA) phosphatase, and its activator Nem1 are highly enriched at this site. The specific accumulation of PA-binding marker proteins indicates a local enrichment of PA in the fld1 and ldb16 mutants. Furthermore, we demonstrate that clustered LD in fld1 or ldb16 mutants are transformed to SLD if phosphatidylcholine synthesis is compromised by additional deletion of the phosphatidylethanolamine methyltransferase, Cho2. Notably, treatment of wild-type cells with oleate induced a similar LD clustering and nuclear membrane proliferation phenotype as observed in fld1 and ldb16 mutants. These data suggest that the Fld1-Ldb16 complex affects PA homeostasis at an LD-forming subdomain of the nuclear envelope. Lack of Fld1-Ldb16 leads to locally elevated PA levels that induce an abnormal proliferation of nER membrane structures and the clustering of associated LD. We suggest that the formation of SLD is a consequence of locally altered PL metabolism at this site. Copyright © 2015. Published by Elsevier B.V.
Find related publications in this database (using NLM MeSH Indexing): Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum - ultrastructure; GTP-Binding Protein gamma Subunits - deficiency; GTP-Binding Protein gamma Subunits - genetics; Gene Expression Regulation, Fungal -; Lipid Droplets - drug effects; Lipid Droplets - metabolism; Lipid Droplets - ultrastructure; Lipid Metabolism - drug effects; Mitochondrial Proteins - deficiency; Mitochondrial Proteins - genetics; Mutation -; Nuclear Envelope - drug effects; Nuclear Envelope - genetics; Nuclear Envelope - metabolism; Nuclear Envelope - ultrastructure; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oleic Acid - pharmacology; Phosphatidate Phosphatase - genetics; Phosphatidate Phosphatase - metabolism; Phosphatidic Acids - metabolism; Phosphatidylcholines - metabolism; Phosphatidylethanolamine N-Methyltransferase - genetics; Phosphatidylethanolamine N-Methyltransferase - metabolism; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae - ultrastructure; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Signal Transduction -
Find related publications in this database (Keywords): Phosphatidate phosphatase; Phosphatidic acid; Diacylglycerol; Seipin; Nuclear envelope; Lipid droplet; Yeast; Saccharomyces cerevisiae

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