%0 Journal Article
%A Chen, Zhiyi
%A Inague, Alex
%A Kaushal, Kamini
%A Fazeli, Gholamreza
%A Schilling, Danny
%A Xavier da Silva, Thamara N
%A Dos Santos, Ancely Ferreira
%A Cheytan, Tasneem
%A Freitas, Florencio Porto
%A Yildiz, Umut
%A Viviani, Lucas Gasparello
%A Lima, Rodrigo Santiago
%A Pinz, Mikaela Peglow
%A Medeiros, Isadora
%A Iijima, Thais Satie
%A Alegria, Thiago Geronimo Pires
%A Pereira da Silva, Railmara
%A Diniz, Larissa Regina
%A Weinzweig, Simon
%A Klein-Seetharaman, Judith
%A Trumpp, Andreas
%A Mañas, Adriana
%A Hondal, Robert
%A Bartenhagen, Christoph
%A Fischer, Matthias
%A Shimada, Briana K
%A Seale, Lucia A
%A Chillon, Thilo Samson
%A Fabiano, Marietta
%A Schomburg, Lutz
%A Schweizer, Ulrich
%A Netto, Luis E
%A Meotti, Flavia C
%A Dick, Tobias P
%A Alborzinia, Hamed
%A Miyamoto, Sayuri
%A Friedmann Angeli, José Pedro
%T PRDX6 contributes to selenocysteine metabolism and ferroptosis resistance.
%J Molecular cell
%V 84
%N 23
%@ 1097-2765
%C New York, NY
%I Elsevier
%M DKFZ-2024-02325
%P  4645–4659.e9
%D 2024
%Z DKFZ-ZMBH Alliance / 84(23), pp. 4645–4659.e9
%X 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.
%K cancer metabolism (Other)
%K cell death (Other)
%K ferroptosis (Other)
%K neuroblastoma (Other)
%K selenium (Other)
%K selenocysteine metabolism (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39547224
%R 10.1016/j.molcel.2024.10.027
%U https://inrepo02.dkfz.de/record/294550