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Saturated fatty acids alter the late secretory pathway by modulating membrane properties.

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  • معلومة اضافية
    • المصدر:
      Publisher: Wiley Country of Publication: England NLM ID: 100939340 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1600-0854 (Electronic) Linking ISSN: 13989219 NLM ISO Abbreviation: Traffic Subsets: MEDLINE
    • بيانات النشر:
      Publication: Oxford : Wiley
      Original Publication: Copenhagen, Denmark ; Malden, MA : Munksgaard, c2000-
    • الموضوع:
      Secretory Pathway*; Cell Membrane/*metabolism ; Fatty Acids/*metabolism ; Saccharomyces cerevisiae/*metabolism; Ceramides/metabolism ; Phospholipids/metabolism ; Transport Vesicles/metabolism ; Unfolded Protein Response ; trans-Golgi Network/metabolism
    • نبذة مختصرة :
      Saturated fatty acids (SFA) have been reported to alter organelle integrity and function in many cell types, including muscle and pancreatic β-cells, adipocytes, hepatocytes and cardiomyocytes. SFA accumulation results in increased amounts of ceramides/sphingolipids and saturated phospholipids (PL). In this study, using a yeast-based model that recapitulates most of the trademarks of SFA-induced lipotoxicity in mammalian cells, we demonstrate that these lipid species act at different levels of the secretory pathway. Ceramides mostly appear to modulate the induction of the unfolded protein response and the transcription of nutrient transporters destined to the cell surface. On the other hand, saturated PL, by altering membrane properties, directly impact vesicular budding at later steps in the secretory pathway, i.e. at the trans-Golgi Network level. They appear to do so by increasing lipid order within intracellular membranes which, in turn, alters the recruitment of loose lipid packing-sensing proteins, required for optimal budding, to nascent vesicles. We propose that this latter general mechanism could account for the well-documented deleterious impacts of fatty acids on the last steps of the secretory pathway in several cell types.
      (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
    • Contributed Indexing:
      Keywords: Arf-GAP1; loose lipid packing; protein trafficking; trans-Golgi network; type 2 diabetes; vesicular budding
    • الرقم المعرف:
      0 (Ceramides)
      0 (Fatty Acids)
      0 (Phospholipids)
    • الموضوع:
      Date Created: 20130917 Date Completed: 20140701 Latest Revision: 20131112
    • الموضوع:
      20231215
    • الرقم المعرف:
      10.1111/tra.12117
    • الرقم المعرف:
      24034583