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Thürmer, Maria; Gollowitzer, André; Pein, Helmut; Neukirch, Konstantin; Gelmez, Elif; Waltl, Lorenz; Wielsch, Natalie; Winkler, René; Löser, Konstantin; Grander, Julia; Hotze, Madlen; Harder, Sönke; Döding, Annika; Meßner, Martina; Troisi, Fabiana; Ardelt, Maximilian; Schlüter, Hartmut; Pachmayr, Johanna; Gutiérrez-Gutiérrez, Óscar; Rudolph, Karl Lenhard; Thedieck, Kathrin; Schulze-Späte, Ulrike; González-Estévez, Cristina; Kosan, Christian; [...]

PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling

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  • Medientyp: E-Artikel
  • Titel: PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling
  • Beteiligte: Thürmer, Maria; Gollowitzer, André; Pein, Helmut; Neukirch, Konstantin; Gelmez, Elif; Waltl, Lorenz; Wielsch, Natalie; Winkler, René; Löser, Konstantin; Grander, Julia; Hotze, Madlen; Harder, Sönke; Döding, Annika; Meßner, Martina; Troisi, Fabiana; Ardelt, Maximilian; Schlüter, Hartmut; Pachmayr, Johanna; Gutiérrez-Gutiérrez, Óscar; Rudolph, Karl Lenhard; Thedieck, Kathrin; Schulze-Späte, Ulrike; González-Estévez, Cristina; Kosan, Christian; [...]
  • Erschienen: Springer Science and Business Media LLC, 2022
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/s41467-022-30374-9
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Cytotoxic stress activates stress-activated kinases, initiates adaptive mechanisms, including the unfolded protein response (UPR) and autophagy, and induces programmed cell death. Fatty acid unsaturation, controlled by stearoyl-CoA desaturase (SCD)1, prevents cytotoxic stress but the mechanisms are diffuse. Here, we show that 1,2-dioleoyl-<jats:italic>sn</jats:italic>-glycero-3-phospho-(1’-myo-inositol) [PI(18:1/18:1)] is a SCD1-derived signaling lipid, which inhibits p38 mitogen-activated protein kinase activation, counteracts UPR, endoplasmic reticulum-associated protein degradation, and apoptosis, regulates autophagy, and maintains cell morphology and proliferation. SCD1 expression and the cellular PI(18:1/18:1) proportion decrease during the onset of cell death, thereby repressing protein phosphatase 2 A and enhancing stress signaling. This counter-regulation applies to mechanistically diverse death-inducing conditions and is found in multiple human and mouse cell lines and tissues of <jats:italic>Scd1</jats:italic>-defective mice. PI(18:1/18:1) ratios reflect stress tolerance in tumorigenesis, chemoresistance, infection, high-fat diet, and immune aging. Together, PI(18:1/18:1) is a lipokine that links fatty acid unsaturation with stress responses, and its depletion evokes stress signaling.</jats:p>
  • Zugangsstatus: Freier Zugang