title: An inducible ER-Golgi tether facilitates ceramide transport to alleviate lipotoxicity.
abstract: Ceramides are key intermediates in sphingolipid biosynthesis and potent signaling molecules. However, excess ceramide is toxic, causing growth arrest and apoptosis. In this study, we identify a novel mechanism by which cells prevent the toxic accumulation of ceramides; they facilitate nonvesicular ceramide transfer from the endoplasmic reticulum (ER) to the Golgi complex, where ceramides are converted to complex sphingolipids. We find that the yeast protein Nvj2p promotes the nonvesicular transfer of ceramides from the ER to the Golgi complex. The protein is a tether that generates close contacts between these compartments and may directly transport ceramide. Nvj2p normally resides at contacts between the ER and other organelles, but during ER stress, it relocalizes to and increases ER-Golgi contacts. ER-Golgi contacts fail to form during ER stress in cells lacking Nvj2p. Our findings demonstrate that cells regulate ER-Golgi contacts in response to stress and reveal that nonvesicular ceramide transfer out of the ER prevents the buildup of toxic amounts of ceramides.
authors.affiliation: Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Li-Ka
authors.identifier: http://orcid.org/0000-0002-2647-2247
authors.initials: LK
authors.lastname: Liu
authors.affiliation: Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Vineet
authors.initials: V
authors.lastname: Choudhary
authors.affiliation: Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 toulmayal@niddk.nih.gov prinzw@helix.nih.gov.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Toulmay
authors.affiliation: Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 toulmayal@niddk.nih.gov prinzw@helix.nih.gov.
authors.forename: William A
authors.identifier: http://orcid.org/0000-0002-9053-2398
authors.initials: WA
authors.lastname: Prinz
mesh_terms: D001692:Biological Transport; D002518:Ceramides / Q000378:metabolism* / Q000633:toxicity*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D005838:Genotype; D006056:Golgi Apparatus / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010641:Phenotype; D000072417:Protein Domains; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D002518:Ceramides; D008565:Membrane Proteins; C581360:Nvj2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins