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PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling
Maria Thürmer1, André Gollowitzer2, Helmut Pein1
1Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, 07743, Jena, Germany.
Nature Communications
|May 27, 2022
Summary
A specific lipid, PI(18:1/18:1), derived from stearoyl-CoA desaturase 1 (SCD1), protects cells from cytotoxic stress by regulating key survival pathways. Its depletion signals cell death, impacting various conditions.
Area of Science:
- Cellular Biology
- Lipid Metabolism
- Stress Response Signaling
Background:
- Cytotoxic stress triggers adaptive mechanisms like the unfolded protein response (UPR) and autophagy, but can lead to programmed cell death.
- Stearoyl-CoA desaturase 1 (SCD1)-mediated fatty acid unsaturation is known to prevent stress, yet the underlying mechanisms remain unclear.
Purpose of the Study:
- To elucidate the role of SCD1-derived lipids in cellular stress responses.
- To identify specific signaling lipids that mediate protection against cytotoxic stress.
- To investigate the link between fatty acid unsaturation and cell survival pathways.
Main Methods:
- Characterization of SCD1-derived lipids and their effects on cellular signaling pathways.
- Analysis of UPR, ER-associated protein degradation, apoptosis, and autophagy markers.
- Assessment of PI(18:1/18:1) levels in various stress conditions and cell types, including Scd1-defective models.
Main Results:
- Identified 1,2-dioleoyl-sn-glycero-3-phospho-(1'-myo-inositol) [PI(18:1/18:1)] as a key SCD1-derived signaling lipid.
- PI(18:1/18:1) inhibits p38 MAPK activation, counteracts UPR, ER-associated protein degradation, and apoptosis, while regulating autophagy.
- Decreased SCD1 expression and PI(18:1/18:1) levels correlate with cell death onset, leading to repressed protein phosphatase 2A and enhanced stress signaling.
Conclusions:
- PI(18:1/18:1) acts as a lipokine linking fatty acid unsaturation to cellular stress tolerance.
- Depletion of PI(18:1/18:1) promotes stress signaling and cell death.
- PI(18:1/18:1) levels serve as indicators of stress tolerance in diverse conditions including tumorigenesis and aging.
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