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@ARTICLE{Tonnus:303496,
author = {W. Tonnus and F. Maremonti and S. Gavali and M. N. Schlecht
and F. Gembardt and A. Belavgeni and N. Leinung and K. Flade
and N. Bethe and S. Traikov and A. Haag and D. Schilling$^*$
and S. Penkov and M. Mallais and C. Gaillet and C. Meyer and
M. Katebi and A. Ray and L. M. S. Gerhardt and A. Brucker
and J. N. Becker and M. Tmava and L. Schlicker$^*$ and A.
Schulze$^*$ and N. Himmerkus and A. Shevchenko and M.
Peitzsch and U. Barayeu and S. Nasi and J. Putz and K. S.
Korach and J. Neugarten and L. Golestaneh and C. Hugo and J.
U. Becker and J. M. Weinberg and S. Lorenz and B. Proneth
and M. Conrad and E. Wolf and B. Plietker and R. Rodriguez
and D. A. Pratt and T. P. Dick$^*$ and M. Fedorova and S. R.
Bornstein and A. Linkermann},
title = {{M}ultiple oestradiol functions inhibit ferroptosis and
acute kidney injury.},
journal = {Nature},
volume = {nn},
issn = {0028-0836},
address = {London [u.a.]},
publisher = {Nature Publ. Group},
reportid = {DKFZ-2025-01687},
pages = {nn},
year = {2025},
note = {DKFZ-ZMBH Alliance / epub},
abstract = {Acute tubular necrosis mediates acute kidney injury (AKI)
and nephron loss1, the hallmark of end-stage renal
disease2-4. For decades, it has been known that female
kidneys are less sensitive to AKI5,6. Acute tubular necrosis
involves dynamic cell death propagation by ferroptosis along
the tubular compartment7,8. Here we demonstrate abrogated
ferroptotic cell death propagation in female kidney tubules.
17β-oestradiol establishes an anti-ferroptotic state
through non-genomic and genomic mechanisms. These include
the potent direct inhibition of ferroptosis by
hydroxyoestradiol derivatives, which function as radical
trapping antioxidants, are present at high concentrations in
kidney tubules and, when exogenously applied, protect male
mice from AKI. In cells, the oxidized hydroxyoestradiols are
recycled by FSP19,10, but FSP1-deficient female mice were
not sensitive to AKI. At the genomic level, female
ESR1-deficient kidney tubules partially lose their
anti-ferroptotic capacity, similar to ovariectomized mice.
While ESR1 promotes the anti-ferroptotic hydropersulfide
system, male tubules express pro-ferroptotic proteins of the
ether lipid pathway which are suppressed by ESR1 in female
tissues until menopause. In summary, we identified
non-genomic and genomic mechanisms that collectively explain
ferroptosis resistance in female tubules and may function as
therapeutic targets for male and postmenopausal female
individuals.},
cin = {A160 / A410},
ddc = {500},
cid = {I:(DE-He78)A160-20160331 / I:(DE-He78)A410-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40804518},
doi = {10.1038/s41586-025-09389-x},
url = {https://inrepo02.dkfz.de/record/303496},
}