TY  - JOUR
AU  - Chen, Zhiyi
AU  - Inague, Alex
AU  - Kaushal, Kamini
AU  - Fazeli, Gholamreza
AU  - Schilling, Danny
AU  - Xavier da Silva, Thamara N
AU  - Dos Santos, Ancely Ferreira
AU  - Cheytan, Tasneem
AU  - Freitas, Florencio Porto
AU  - Yildiz, Umut
AU  - Viviani, Lucas Gasparello
AU  - Lima, Rodrigo Santiago
AU  - Pinz, Mikaela Peglow
AU  - Medeiros, Isadora
AU  - Iijima, Thais Satie
AU  - Alegria, Thiago Geronimo Pires
AU  - Pereira da Silva, Railmara
AU  - Diniz, Larissa Regina
AU  - Weinzweig, Simon
AU  - Klein-Seetharaman, Judith
AU  - Trumpp, Andreas
AU  - Mañas, Adriana
AU  - Hondal, Robert
AU  - Bartenhagen, Christoph
AU  - Fischer, Matthias
AU  - Shimada, Briana K
AU  - Seale, Lucia A
AU  - Chillon, Thilo Samson
AU  - Fabiano, Marietta
AU  - Schomburg, Lutz
AU  - Schweizer, Ulrich
AU  - Netto, Luis E
AU  - Meotti, Flavia C
AU  - Dick, Tobias P
AU  - Alborzinia, Hamed
AU  - Miyamoto, Sayuri
AU  - Friedmann Angeli, José Pedro
TI  - PRDX6 contributes to selenocysteine metabolism and ferroptosis resistance.
JO  - Molecular cell
VL  - 84
IS  - 23
SN  - 1097-2765
CY  - New York, NY
PB  - Elsevier
M1  - DKFZ-2024-02325
SP  -  4645–4659.e9
PY  - 2024
N1  - DKFZ-ZMBH Alliance / 84(23), pp. 4645–4659.e9
AB  - 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.
KW  - cancer metabolism (Other)
KW  - cell death (Other)
KW  - ferroptosis (Other)
KW  - neuroblastoma (Other)
KW  - selenium (Other)
KW  - selenocysteine metabolism (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39547224
DO  - DOI:10.1016/j.molcel.2024.10.027
UR  - https://inrepo02.dkfz.de/record/294550
ER  -