Details

Autor(en) / Beteiligte

• Freitas, Florencio Porto
• Alborzinia, Hamed
• Dos Santos, Ancély Ferreira
• Nepachalovich, Palina
• Pedrera, Lohans
• Zilka, Omkar
• Inague, Alex
• Klein, Corinna
• Aroua, Nesrine
• Kaushal, Kamini
• Kast, Bettina
• Lorenz, Svenja M
• Kunz, Viktoria
• Nehring, Helene
• Xavier da Silva, Thamara N
• Chen, Zhiyi
• Atici, Sena
• Doll, Sebastian G
• Schaefer, Emily L
• Ekpo, Ifedapo
• Schmitz, Werner
• Horling, Aline
• Imming, Peter
• Miyamoto, Sayuri
• Wehman, Ann M
• Genaro-Mattos, Thiago C
• Mirnics, Karoly
• Kumar, Lokender
• Klein-Seetharaman, Judith
• Meierjohann, Svenja
• Weigand, Isabel
• Kroiss, Matthias
• Bornkamm, Georg W
• Gomes, Fernando
• Netto, Luis Eduardo Soares
• Sathian, Manjima B
• Konrad, David B
• Covey, Douglas F
• Michalke, Bernhard
• Bommert, Kurt
• Bargou, Ralf C
• Garcia-Saez, Ana
• Pratt, Derek A
• Fedorova, Maria
• Trumpp, Andreas
• Conrad, Marcus
• Friedmann Angeli, José Pedro

Titel

7-Dehydrocholesterol is an endogenous suppressor of ferroptosis

Ist Teil von

• Nature (London), 2024-02, Vol.626 (7998), p.401-410

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• Ferroptosis is a form of cell death that has received considerable attention not only as a means to eradicate defined tumour entities but also because it provides unforeseen insights into the metabolic adaptation that tumours exploit to counteract phospholipid oxidation . Here, we identify proferroptotic activity of 7-dehydrocholesterol reductase (DHCR7) and an unexpected prosurvival function of its substrate, 7-dehydrocholesterol (7-DHC). Although previous studies suggested that high concentrations of 7-DHC are cytotoxic to developing neurons by favouring lipid peroxidation , we now show that 7-DHC accumulation confers a robust prosurvival function in cancer cells. Because of its far superior reactivity towards peroxyl radicals, 7-DHC effectively shields (phospho)lipids from autoxidation and subsequent fragmentation. We provide validation in neuroblastoma and Burkitt's lymphoma xenografts where we demonstrate that the accumulation of 7-DHC is capable of inducing a shift towards a ferroptosis-resistant state in these tumours ultimately resulting in a more aggressive phenotype. Conclusively, our findings provide compelling evidence of a yet-unrecognized antiferroptotic activity of 7-DHC as a cell-intrinsic mechanism that could be exploited by cancer cells to escape ferroptosis.