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@ARTICLE{Chen:294550,
author = {Z. Chen and A. Inague and K. Kaushal$^*$ and G. Fazeli and
D. Schilling$^*$ and T. N. Xavier da Silva and A. F. Dos
Santos and T. Cheytan$^*$ and F. P. Freitas and U. Yildiz
and L. G. Viviani and R. S. Lima and M. P. Pinz and I.
Medeiros and T. S. Iijima and T. G. P. Alegria and R.
Pereira da Silva and L. R. Diniz and S. Weinzweig and J.
Klein-Seetharaman and A. Trumpp$^*$ and A. Mañas and R.
Hondal and C. Bartenhagen and M. Fischer and B. K. Shimada
and L. A. Seale and T. S. Chillon and M. Fabiano and L.
Schomburg and U. Schweizer and L. E. Netto and F. C. Meotti
and T. P. Dick$^*$ and H. Alborzinia$^*$ and S. Miyamoto and
J. P. Friedmann Angeli},
title = {{PRDX}6 contributes to selenocysteine metabolism and
ferroptosis resistance.},
journal = {Molecular cell},
volume = {84},
number = {23},
issn = {1097-2765},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DKFZ-2024-02325},
pages = {4645–4659.e9},
year = {2024},
note = {DKFZ-ZMBH Alliance / 84(23), pp. 4645–4659.e9},
abstract = {Selenocysteine (Sec) metabolism is crucial for cellular
function and ferroptosis prevention and begins with the
uptake of the Sec carrier, selenoprotein P (SELENOP).
Following uptake, Sec released from SELENOP is metabolized
via selenocysteine lyase (SCLY), producing selenide, a
substrate for selenophosphate synthetase 2 (SEPHS2), which
provides the essential selenium donor, selenophosphate
(H2SePO3-), for the biosynthesis of the Sec-tRNA. Here, we
discovered an alternative pathway in Sec metabolism mediated
by peroxiredoxin 6 (PRDX6), independent of SCLY.
Mechanistically, we demonstrate that PRDX6 can readily react
with selenide and interact with SEPHS2, potentially acting
as a selenium delivery system. Moreover, we demonstrate the
functional significance of this alternative route in human
cancer cells, revealing a notable association between
elevated expression of PRDX6 and human MYCN-amplified
neuroblastoma subtype. Our study sheds light on a previously
unrecognized aspect of Sec metabolism and its implications
in ferroptosis, offering further possibilities for
therapeutic exploitation.},
keywords = {cancer metabolism (Other) / cell death (Other) /
ferroptosis (Other) / neuroblastoma (Other) / selenium
(Other) / selenocysteine metabolism (Other)},
cin = {A010 / A160},
ddc = {610},
cid = {I:(DE-He78)A010-20160331 / I:(DE-He78)A160-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39547224},
doi = {10.1016/j.molcel.2024.10.027},
url = {https://inrepo02.dkfz.de/record/294550},
}