Reference - Detail
| RRC ID | 83158 |
|---|---|
| Author | Gollowitzer A, Pein H, Rao Z, Waltl L, Bereuter L, Loeser K, Meyer T, Jafari V, Witt F, Winkler R, Su F, Große S, Thürmer M, Grander J, Hotze M, Harder S, Espada L, Magnutzki A, Gstir R, Weinigel C, Rummler S, Bonn G, Pachmayr J, Ermolaeva M, Harayama T, Schlüter H, Kosan C, Heller R, Thedieck K, Schmitt M, Shimizu T, Popp J, Shindou H, Kwiatkowski M, Koeberle A. |
| Title | Attenuated growth factor signaling during cell death initiation sensitizes membranes towards peroxidation. |
| Journal | Nat Commun |
| Abstract |
Cell death programs such as apoptosis and ferroptosis are associated with aberrant redox homeostasis linked to lipid metabolism and membrane function. Evidence for cross-talk between these programs is emerging. Here, we show that cytotoxic stress channels polyunsaturated fatty acids via lysophospholipid acyltransferase 12 into phospholipids that become susceptible to peroxidation under additional redox stress. This reprogramming is associated with altered acyl-CoA synthetase isoenzyme expression and caused by a decrease in growth factor receptor tyrosine kinase (RTK)-phosphatidylinositol-3-kinase signaling, resulting in suppressed fatty acid biosynthesis, for specific stressors via impaired Akt-SREBP1 activation. The reduced availability of de novo synthesized fatty acids favors the channeling of polyunsaturated fatty acids into phospholipids. Growth factor withdrawal by serum starvation mimics this phenotype, whereas RTK ligands counteract it. We conclude that attenuated RTK signaling during cell death initiation increases cells' susceptibility to oxidative membrane damage at the interface of apoptosis and alternative cell death programs. |
| Volume | 16(1) |
| Pages | 1774 |
| Published | 2025-2-25 |
| DOI | 10.1038/s41467-025-56711-2 |
| PII | 10.1038/s41467-025-56711-2 |
| PMID | 40000627 |
| PMC | PMC11861335 |
| MeSH | Animals Apoptosis* Cell Death Cell Membrane / metabolism Coenzyme A Ligases / genetics Coenzyme A Ligases / metabolism Fatty Acids, Unsaturated / metabolism Ferroptosis Humans Lipid Peroxidation* Oxidation-Reduction Oxidative Stress Phosphatidylinositol 3-Kinases / metabolism Phospholipids / metabolism Proto-Oncogene Proteins c-akt / metabolism Signal Transduction* Sterol Regulatory Element Binding Protein 1 / genetics Sterol Regulatory Element Binding Protein 1 / metabolism |
| IF | 12.121 |
| Resource | |
| Human and Animal Cells | Hepa 1-6(RCB1638) |