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869186.pdf (3.07 MB)

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2022-05-27

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cc-by (c) Thürmer M et al., 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/216695

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

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Recurs relacionat

https://doi.org/doi: 10.1038/s41467-022-30374-9

Resum

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-phos- pho-(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.

Matèries

Proteïnes quinases, Estrès (Fisiologia), Autofàgia

Matèries (anglès)

Protein kinases, Stress (Physiology), Autophagy

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Articles publicats en revistes (Genètica, Microbiologia i Estadística)
Articles publicats en revistes (Institut de Biomedicina (IBUB))

Citació

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, SVATOŠ, Aleš, KWIATKOWSKI, Marcel, KOEBERLE, Andreas. PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling. _Nature Communications_. 2022. Vol. 13, núm. 1, pàgs. 1-21. [consulta: 7 de gener de 2026]. ISSN: 2041-1723. [Disponible a: https://hdl.handle.net/2445/216695]

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