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

Author

Listed:
  • Maria Thürmer

    (Friedrich-Schiller-University Jena)

  • André Gollowitzer

    (University of Innsbruck)

  • Helmut Pein

    (Friedrich-Schiller-University Jena)

  • Konstantin Neukirch

    (University of Innsbruck)

  • Elif Gelmez

    (Friedrich-Schiller-University Jena)

  • Lorenz Waltl

    (University of Innsbruck)

  • Natalie Wielsch

    (Max Planck Institute for Chemical Ecology)

  • René Winkler

    (Friedrich-Schiller-University Jena)

  • Konstantin Löser

    (Friedrich-Schiller-University Jena)

  • Julia Grander

    (University of Innsbruck)

  • Madlen Hotze

    (University of Innsbruck)

  • Sönke Harder

    (University Medical Center Hamburg-Eppendorf)

  • Annika Döding

    (University Hospital Jena, Friedrich-Schiller-University Jena)

  • Martina Meßner

    (Pharmaceutical Biology, LMU Munich
    Paracelsus Medical University)

  • Fabiana Troisi

    (Friedrich-Schiller-University Jena)

  • Maximilian Ardelt

    (Pharmaceutical Biology, LMU Munich
    Paracelsus Medical University)

  • Hartmut Schlüter

    (University Medical Center Hamburg-Eppendorf)

  • Johanna Pachmayr

    (Pharmaceutical Biology, LMU Munich
    Paracelsus Medical University)

  • Óscar Gutiérrez-Gutiérrez

    (Leibniz Institute on Aging—Fritz Lipmann Institute (FLI))

  • Karl Lenhard Rudolph

    (Leibniz Institute on Aging—Fritz Lipmann Institute (FLI))

  • Kathrin Thedieck

    (University of Innsbruck
    University of Groningen, University Medical Center Groningen
    Carl von Ossietzky University Oldenburg)

  • Ulrike Schulze-Späte

    (University Hospital Jena, Friedrich-Schiller-University Jena)

  • Cristina González-Estévez

    (Leibniz Institute on Aging—Fritz Lipmann Institute (FLI)
    University of Barcelona
    Institute of Biomedicine of the University of Barcelona (IBUB))

  • Christian Kosan

    (Friedrich-Schiller-University Jena)

  • Aleš Svatoš

    (Max Planck Institute for Chemical Ecology)

  • Marcel Kwiatkowski

    (University of Innsbruck)

  • Andreas Koeberle

    (Friedrich-Schiller-University Jena
    University of Innsbruck)

Abstract

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-sn-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 Scd1-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.

Suggested Citation

  • Maria Thürmer & André Gollowitzer & Helmut Pein & Konstantin Neukirch & Elif Gelmez & Lorenz Waltl & Natalie Wielsch & René Winkler & Konstantin Löser & Julia Grander & Madlen Hotze & Sönke Harder & A, 2022. "PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30374-9
    DOI: 10.1038/s41467-022-30374-9
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    References listed on IDEAS

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    1. Samim Sharifi & Prerana Chaudhari & Asya Martirosyan & Alexander Otto Eberhardt & Finja Witt & André Gollowitzer & Lisa Lange & Yvonne Woitzat & Eberechukwu Maryann Okoli & Huahui Li & Norman Rahnis &, 2024. "Reducing the metabolic burden of rRNA synthesis promotes healthy longevity in Caenorhabditis elegans," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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